Hexylamine

Endpoint summary

Description of key information

oral:
The oral LD50 value of the test substance was determined to be 240 mg/kg bw.
inhalation:
After 3 min exposure to 74.67 mg test substance /L air no animals died, after 10 minutes 5 of 6 animals were dead.
dermal:
In a dermal toxicity study on rabbits the LD50 of the test substance was determined to be 420 mg/kg bw.
intraperitoneal:
After intraperitoneal administration, the LD50 of the test substance was determined to be 53 mg/kg bw.

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically acceptable study report, comparable to guideline with acceptable restrictions (due to reduced reporting in times before GLP).

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

only 7 days observation period

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Willi Gassner, Sulzfeld, Germany
- Age at study initiation: young adults
- Mean weight at study initiation (± SD): males: 168.4 ± 29 g, females: 139.8 ± 18 g

Route of administration:

oral: gavage

Vehicle:

other: aqueous emulsion containing Traganth

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2; 4; 8 and 20 % (v/v)
- Amount of vehicle: 8; 10; 12.5; 16 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg bw

Doses:

200; 250; 320; 400; 800; 1600 µL/kg bw (corresponding to 152.84, 191.05, 244.54, 305.68, 611.36, 1222.72 mg/kg bw; calculated using the density of 0.7642)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Body weight was determined before the beginning of the study for dose calculation.
- Other examinations performed: Observation of clinical signs was several times on the day of administration and once daily afterwards with the exception of weekends and on holidays.
- Necropsy of survivors performed: yes

Statistics:

On the basis of the observed lethality, the LD50 value was estimated or determined using a graphical evaluation of the dose response curve on probability paper.

Sex:

male/female

Dose descriptor:

approximate LD50

Effect level:

ca. 244 mg/kg bw

Based on:

test mat.

Remarks on result:

other: corresponding to the original value of ca. 320 mm3, calculated with density of 0.7642

Mortality:

Results are given as dead animals/total number of animals at this dose at 1 h / 24 h / 48 h / 7 days after dosing:
Males
153 mg/kg bw: 0/10, 0/10, 0/10, 0/10
192 mg/kg bw: 0/10, 0/10, 0/10, 0/10
245 mg/kg bw: 0/10, 1/10, 0/10, 0/10
306 mg/kg bw: 0/10, 7/10, 7/10, 7/10
613 mg/kg bw: 10/10, 10/10, 10/10, 10/10
1226 mg/kg bw: 10/10, 10/10, 10/10, 10/10

Females
153 mg/kg bw: 0/10, 0/10, 0/10, 0/10
192 mg/kg bw: 0/10, 2/10, 2/10, 2/10
245 mg/kg bw: 1/10, 4/10, 4/10, 4/10
306 mg/kg bw: 0/10, 10/10, 10/10, 10/10
613 mg/kg bw: 10/10, 10/10, 10/10, 10/10
1226 mg/kg bw: 10/10, 10/10, 10/10, 10/10

Clinical signs:

other: 153 mg/kg bw: Approximately 5 min after gavage crouched position, apathy and shallow respiration were observed. On the following days no abnormalites were detected. 192 - 245 mg/kg bw: Immediately after gavage increased disposition to develop convulsions,

Gross pathology:

Sacrificed animals: no abnormality detected.

Other findings:

No other fndings

Table 1 Acute oral toxicity

 

Dose* [mg/kg bw]	Mortality
	N	%	Time of death
Males
152.84	0/10	0	-
191.05	0/10	0	-
244.54	1/10	10	Within 24 hours
305.68	7/10	70	Within 24 hours
611.36	10/10	100	Within 24 hours
1222.72	10/10	100	Within 1 hour
Females
152.84	0/10	0	-
191.05	2/10	20	Within 24 hours
244.54	4/10	40	Within 1 to 24 hours
305.68	10/10	100	Within 24 hours
611.36	10/10	100	Within 24 hours
1222.72	10/10	100	Within 1 hour

* original doses (200, 250, 320, 400, 800 and 1600 mm3) converted using the densitiy of 0.7642

N= number of dead animals / number of animals used

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

244 mg/kg bw

Quality of whole database:

Scientifically acceptable study report, comparable to guideline with acceptable restrictions (mostly due to reduced reporting in times before GLP).

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: sufficient for classification with restrictions (short exposure times)

Principles of method if other than guideline:

according to BASF-internal standard

GLP compliance:

no

Test type:

other: inhalation hazard test

Species:

rat

Strain:

not specified

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

not specified

Analytical verification of test atmosphere concentrations:

not specified

Remarks on duration:

3 min and 10 min

Concentrations:

74.67 mg/L

No. of animals per sex per dose:

3 min: 12
10 min: 6

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LC0

Effect level:

74.67 mg/L air

Based on:

test mat.

Exp. duration:

3 min

Sex:

male/female

Dose descriptor:

LC50

Effect level:

< 74.67 mg/L air

Based on:

test mat.

Exp. duration:

10 min

Mortality:

3 min exposure: no deaths
10 min exposure: 5/6

Clinical signs:

other: severe attempt to escape, intense reddening of the mucosa, dyspnea, breathlessness, at the end of the study trembling

Body weight:

no data

Gross pathology:

bloody-serous blurred snouts, cloudings of the breaking media of the eyes

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Quality of whole database:

orientating information of inhalation toxicity, inhalation exposure time only 10 minutes, extrapolation of an exact LD50 (4h) is not possible

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Scientifically acceptable.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

not specified

Vehicle:

not specified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

420 mg/kg bw

Based on:

test mat.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

420 mg/kg bw

Quality of whole database:

Old publication, but sufficient for assessment.

Additional information

Oral:

In a study conducted similar to OECD Guideline 401, the acute toxicity of the test substance to rats after oral administration was assessed. 10 rats per sex per dose were used, doses were chosen as follows: 200, 250, 320, 400, 800, 1600 µL/kg bw (corresponding to 153, 192, 245, 306, 613, 1226 mg/kg bw; calculated using the density of 0.766 g/cm2 at 20°C). Clinical signs observed in the 153 mg/kg bw dose group were crouched position, apathy and shallow respiration approximately 5 min after gavage. On the following days no abnormalites were detected. In the 192 - 245 mg/kg bw dose groups, immediately after gavage increased disposition to develop convulsions, apathy, salivation, exophthalmos and ruffled fur were observed. On the following days sedate behaviour and scrubby fur was recorded. From day 8 onwards no abnormalities detected. In the higher dose groups (306 - 1226 mg/kg bw), immediately after gavage piloerection, convulsions and tremor, salivation and dyspnea were observed. On the following days the surviving animals of the 306 mg/kg bw group exhibited scrubby fur, intermittent respiration and restlessness. The animals appeared normal on day 6. Deaths occurred from the 192 mg/kg bw group onwards in females and from 245 mg/kg bw onwards in males. Based on these results, the LD50 value was determined to be approximately 245 mg/kg bw.

Data provided by the Toxic Substances Control Act Test Submission (TSCATS) database state a LD50 of 670 mg/kg in rats.

In a publication (Hine et al., 1960), a LD50 of 670 mg/kg bw was reported for rats. As a calculation result, a LD50 of 422 mg/kg bw is reported (Jäckel & Klein 1991). A calculated LD50 of 915 mg/kg bw is reported in Enslein et al., 1987. Verschueren (1983) reported a LD50 value of 390 mg/kg bw.

Inhalation:

In an acute inhalation study, rats were exposed to the test substance at a concentration of 74.67 mg/L air for an exposure duration of 3 and 10 min. In the 3 min exposure group, no deaths occurred. In the 10 minutes exposure group, 5 of 6 animals died. Therefore, the LD50 (10 min) of the test substance was found to be < 74.67 mg/L air. Therefore it can be concluded that the LD50 (4h) is also <74.67 mg/L air, but it is not possible to determine an exact value on the basis of the 10 min-exposure results.

The following data were not used for assessment either due to their result types, which are not suitable for classification purposes.

In a publication (Gagnaire, 1993) a study is described in which, for the investigation of the upper airway irritation, the breathing frequency was used as an index. The respiratory rate was measured in oronasally exposed mice by enclosing the head in the inhalation chamber. Exposure concentrations were 0.06, 0.12, 0,19 and 0.27 mg/L. The monitoring of breath frequency was performed with a pressure transducter before and during exposure. Exposure duration was 60 min. 6 mice per test concentration were used. The onset of the maximal response was rapid (1 min.). The effect was steady during the whole exposure time and recovery was rapid and concentration-dependent. The derived RD50 (concentration producing a 50% decrease in respiratory frequency) value was 0.18 mg/L.

For the investigation of the lower airway irritation and the pulmonary toxicity, mice were exposed via tracheal cannnulation and the respiratory rate was measured, as described by Gagnaire (1993). The mice were anaesthetized and a polyethylene cannula was inserted in the trachea and secured. The mice were allowed to recover before starting the experiment. Exposure duration was 120 min. 6 mice per test concentration were used. As a result, the RD50 TC values were determined to be 0.39 mg/L air.

For the investigation of the upper airway irritation, the breathing frequency was used as an index. The respiratory rate was measured in oronasally exposed mice by enclosing the head in the inhalation chamber. The decrease in respiratory rate results from bradypnoea, which is characterized by a typical pause before exhalation and which occurs as a reflexe from the stimulation of the trigeminal nerves ending in the nasal mucosa. The monitoring of breath frequency was performed with a pressure transducter before and during exposure. Exposure duration was 30 min., followed by a 20 min recovery period. 4 mice per test concentration were used. RD50 and RD0 were calculated to be 0.21 and 2.1 mg/L air, respectively.

For the investigation of the lower airway irritation and the pulmonary toxicity, mice were exposed via tracheal cannulation and the respiratory rate was measured. To exclude development of sensory irritation (bradypnoea), the endings of the nasal trigeminal nerve were bypassed. The decrease in respiratory rate related to irritation of the lower airways is characterized by a typical pause between the end of expiration and the beginning of the following inspiration, as a reflexive induction resulting from the stimulation of the pulmonary receptors. Exposure duration was 30 min. 4 mice per test concentration were used. RD50 and RD0 were calculated to be 0.28 and 0.1 mg/L, respectively.

Handbook data (Verschueren, 1983) are also available reporting a 4 hours LCLo value of 2.1 mg/L air. Saturated vapour did not lead to mortality during a 1 hour-exposure.

Dermal:

A publication is available on hexylamine describing a dermal toxicity test on rabbits. The LD50 determined in this study was 420 mg/kg bw. The same LD50 value is reported in the secod study record, which is information obtained from the Toxic Substances Control Act Test Submission (TSCATS) database.

Other routes:

The test substance was tested for its acute toxicity after intraperitoneal application. Therefore concentrations of 0.5, 1, 2 and 20% (v/v) n-hexylamine in water were applied to 10 mice per dose at the following doses: 19, 38, 49, 61, 76, 95, 153, 1221 mg/kg bw. The LD50 was determined to be approximately 53 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
most reliable study available

Justification for selection of acute toxicity – inhalation endpoint
most reliable study available

Justification for selection of acute toxicity – dermal endpoint
One study and one publication were used in a weight of evidence approach for evaluation of the dermal toxicity of the test substance.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is considered to be classified and labelled with R21/22 (harmful in contact with skin and if swallowed) under Directive 67/548/EEC, as amended for the 31st time in Directive 2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered to be classified for acute oral and dermal toxicity cat. 3 and labelled with H301 (Toxic if swallowed) and H311 (Toxic in contact with skin) under Regulation (EC) No 1272/2008, as amended for the sixth time in Regulation EC 605/2014.