12-hydroxyoctadecanoic acid, reaction products with 1,3-benzenedimethanamine and hexamethylenediamine

Endpoint summary

Description of key information

E96095 is not classified according to the CLP Regulation (1272/2008) as LD50 was found to be higher than 2000 mg/kg b.w. for both acute oral toxicity and acute dermal toxicity . 
E96095 is classified as harmful by inhalation (R20) according to the Directive 67/548/CEE and in the Category IV according to the CLP Regulation (1272/2008) for acute inhalation toxicity as LC50 was 5.08 mg/L for rat combined sex corresponding to 3.56 mg/L when considering the respirable particles (< 7 µm diameter).

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)

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

The lowest value recorded for humidity (24%) was outside the range of 30-70%

Principles of method if other than guideline:

Not relevant

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Table 7.2.1/1: signs of reaction to treatment

Clinical signs	No. of rats in groups of 3 showing signs
	Dose (mg/kg b.w.)
	2000
	M	F
Piloerection	3	3
Hunched posture	3	3
Abnormal faeces	0	1
Ungroomed appearance	0	1

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study complete and sufficient to fulfill the endpoint requirements.

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:

1 (reliable without restriction)

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Principles of method if other than guideline:

Not applicable

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Sex:

male

Dose descriptor:

LC50

Effect level:

3.97 mg/L air (analytical)

95% CL:

>= 2.25 - <= 5.69

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

7.42 mg/L air (analytical)

95% CL:

>= -4.75 - <= 19.6

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

5.08 mg/L air (analytical)

95% CL:

>= 1.9 - <= 8.27

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

2.79 other: mg/L (respirable component, i.e. < 7µm)

95% CL:

>= 1.73 - <= 3.85

Exp. duration:

4 h

Sex:

female

Dose descriptor:

LC50

Effect level:

5.03 other: mg/L (respirable component, i.e. < 7 µm))

95% CL:

>= -2.47 - <= 12.53

Exp. duration:

4 h

Sex:

male/female

Dose descriptor:

LC50

Effect level:

3.56 other: mg/L (respirable component, i.e. < 7 µm)

95% CL:

>= 1.47 - <= 5.64

Exp. duration:

4 h

Table 7.2.2/3: lung weights in decedents and 14 days after exposure in survivors

Group	Lung weight
	Males		Females
	Decedent	Survivor	Decedent	Survivor
Control		1.77 ± 0.100		1.31 ± 0.090
0.77 mg/L		1.81 ± 0.119		1.43 ± 0.116
2.26 mg/L		1.83 ± 0.197	2.89	1.50 ± 0.115
5.30 mg/L	1.75	3.66 ± 0.429	3.18	2.47 ± 0.266

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LC50

Value:

3 560 mg/m³ air

Quality of whole database:

Study complete and sufficient to fulfill the endpoint requirements.

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

Reliability:

1 (reliable without restriction)

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

humidity value below the range (24 %)

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Principles of method if other than guideline:

Not applicable

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

occlusive

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Table 7.2.3./2: Number of animals dead and number with evident toxicity

Dose (mg/kg bw)	Conc. In vehicle (% w/v)	Mortality (dead/total)			Time range of deaths (hours)	Number with evident toxicity
		Male	Female	Combined		Male	Female	Combined
2000	50	0	0	0	-	0	0	0

Table 7.2.3./3: Mean irritant/corrosive data at 24, 48 and 72 -hour observations

Score at time point / Reversibility	Erythema (mean score) Max. score: 4	Edema (mean score) Max. score: 4
24 h	1.2	0.9
48 h	0.6	0.3
72 h	0.4	0.3
Average 24h, 48h, 72h	0.73	0.5
Reversibility	c*	c*
Average time (unit) for reversion	Day 7	Day 7

c =completely reversible

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Study complete and sufficient to fulfill the endpoint requirements.

Additional information

E96095 was tested for acute oral toxicity according to OECD 423 guideline and in compliance with GLP. Groups of rats (3 /sex) were administered by gavage a single dose of E96095 at 2000 mg/kg b.w.. No mortality was observed throughout the 14-day observation period. Body weight gain was not affected by treatment. At necropsy, macroscopic examination of main organs showed no abnormalities.

E96095 was tested for acute dermal toxicity in CD Sprague-Dawley rats in a limit dose assay performed according to OECD guideline No 402 in compliance with GLP. Groups of rats (5/sex) were administered a single dermal dose of E96095 at 2000 mg/kg b.w. in corn oil. No death and clinical sign occurred during the 14-day observation period.

E96095 was tested for acute inhalation toxicity in rats according to a protocol similar to OECD 403 guideline in compliance with GLP. The assay was conducted on groups of rats (5/sex) exposed for at 0, 0.77, 2.26 and 5.30 mg/L particulate aerosol for 4 hours. Fast breathing rate, strong mortality (6/10 animals) and increased lung weights compared to controls were observed in the highest dose group. The acute inhalation LD50 for E96095 particle aerosol was 5.08 mg/L for rat combined sex corresponding to 3.56 mg/L when considering the respirable particles (< 7 µm diameter).

Justification for selection of acute toxicity – oral endpoint
Study performed according to the OECD guideline 423 and GLP compliant.

Justification for selection of acute toxicity – inhalation endpoint
Study performed according to the OECD guideline 403 and GLP compliant.

Justification for selection of acute toxicity – dermal endpoint
Study performed according to the OECD guideline 402 and GLP compliant.

Justification for classification or non-classification

As no mortality was observed at 2000 mg/kg b.w. in an acute oral toxicity study performed according to OECD 423 guideline and in compliance with GLP, E96095 is not classified for acute oral toxicity according to the Annex VI to the CLP Regulation (1272/2008).

As no death and clinical sign was observed at 2000 mg/kg b.w. in an acute dermal toxicity study performed according to OECD 402 guideline and in compliance with GLP, E96095 is not classified for acute dermal toxicity according to the Annex VI to the CLP Regulation (1272/2008).

As LC50 for E96095 acute inhalation particle aerosol was 5.08 mg/L for rat combined sex corresponding to 3.56 mg/L when considering the respirable particles (< 7 µm diameter), E96095 is classified as harmful by inhalation (R20) and in the Category IV according to the Annex VI to the CLP Regulation (1272/2008).