Octadecanoic acid, reaction products with diethylenetriamine and urea, acetates

Endpoint summary

Description of key information

Key study was performed according to OECD TG 420 following GLP reports in rats. The results showed a  LD50 of  >2000 mg/kg/d. Whereas, Support study performed in the year 1975 with no test guideline and GLP records in rats showed a LD50  of >5000 mg/kg body weight.

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:

supporting study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

Sample Designation: Ceranin PNA fest

Species:

rat

Strain:

other: CFY strain

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 100 to 112 g
- Fasting period before study: overnight

IN-LIFE DATES: From: May 1975 To: June 1975

Route of administration:

oral: gavage

Vehicle:

other: aqueous gum tragacanth (0.5 %)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 %
- Amount of vehicle (if gavage): 12.5 mL/kg body weight

MAXIMUM DOSE VOLUME APPLIED: 12.5 mL/kg body weight

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

10 rats (5 male and 5 female)

Control animals:

yes

Remarks:

Aqueous gum tragacanth (0.5%) alone (12.5 mL/kg)

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0, 7, 14 day
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs, body weight.

Statistics:

None

Preliminary study:

Ten rats (five male and five female ) were treated wÍth Ceranin PNA fest at a dosage level of 5000 mg/kg body weight.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

Male rats: 2/5 and female rats: 0/5
Death occurred in 2 male rats within five to six days of treatment. Autopsy did not reveal any specific cause of death.

Clinical signs:

other: Lethargy and piloerection.

Gross pathology:

Normal

Other findings:

None

Mortality ratio and group mean body weights (S) of rats dosed orally with Ceranin PNA Fest

Sex	Dosage (g/kg)	Bodyweight (g) at			Mortaility ratio (no of deaths / No dosed)	Time of death after dosing (days)
		Dosing	1 Week	2 Week
Male	0	102	157	239	0/5	-
	5	106	166	241	2/5	< 6
Female	0	108	159	190	0/5	-
	5	102	154	185	0/5	-

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal oral dose (LD50) to rats of Ceranin PNA fest was found to be >5000 mg/kg bodyweight.

Executive summary:

Acute Oral Toxicity of Ceranin PNA fest was evaluated based on a in-house study similar to OECD 401 TG.

Ceranin PNA fest was prepared as a 40 % suspension in aqueous gum tragacanth (0.5 %) and administered by oral intubation at a dosage volume of 12.5 ml/ kg body weight to 10 rats (5 male and 5 female) of the CFY strain in the weight range of 100 to 112 g were treated with Ceranin PNA fest at a dosage level of 5 g/kg bodyweight.

During the observation period of 14 days, a record was kept of all mortalities and signs of toxicity. All rats that died were examined macroscopically in an attempt to identify organs, and those animals surviving terminally were similarly examined to detect possible residual damage.

Signs of reaction to treatment observed shortly after dosing consisted of lethargy and piloerection. Death occurred in two male rats within five to six days of treatment. Autopsy did not reveal any specific cause of death. Recovery of survivors, as judged by external appearance and behaviour, was apparently complete within seven days of treatment. This observation was substantiated by normal bodyweight gains, compared with controls and normal autopsy findings.

The acute median lethal oral dose (LD50) to rats of Ceranin PNA fest was found to be >5000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study technically not feasible

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not 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

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study was performed according to OECD TG 420 for acute oral toxicity by fixed dose method. Four female Wistar rats were treated by oral gavage with test substance FAT 93580 to determine median lethal concentration (LD50).

At the highest test dose of 2000 mg/kg bw all animals survived until the end of the study period and no signs of systemic toxicity were noted during the observation period. All animals showed expected gains in body weight over the observation period and no abnormalities were noted at necropsy.

Another, single acute oral,14-day supporting study was performed with a high dose of 5000 mg/kg bw. Death occurred in two male rats within five to six days of treatment. Autopsy did not reveal any specific cause of death. Recovery of survivors, as judged by external appearance and behaviour, was apparently complete within seven days of treatment. This observation was substantiated by normal bodyweight gains, compared with controls and normal autopsy findings.

Based on the LD50 value and exposure related observations from both the studies the acute oral median lethal dose (LD50) of the test item can be concluded to be greater than 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
The study was conducted according to OECD guideline 420 and in accordance with GLP

Justification for selection of acute toxicity – inhalation endpoint
Waiver: Not necessary, based on the physical form, no exposure through inhalation expected
Currently no study to assess the acute inhalation toxicity potential of FAT 93580/A TE is available. However, the vapour pressure of test item at 25 °C, using the vapour pressure balance method was determined to be 2.6 mPa. Hence, the substance is considered to have low volatility. Synthesis and spray drying of this chemical is performed in a closed process; the final product consists of non-dusty granules. Hence, 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. Further results of exposure to test animals from the acute toxicity studies via oral route with FAT 93580/A TE indicated low toxicity potential and no classification was needed for acute toxicity or STOT SE. Taking into consideration the above arguments, no elevated toxicity other than already seen in acute oral toxicity studies is expected via the inhalation route and safety for human health can be estimated using the principles of route to route extrapolation. Hence, the conduct of acute toxicity study via inhalation route for FAT 93580/A TE is considered to be scientifically not necessary.

Justification for selection of acute toxicity – dermal endpoint
Waiver: Not necessary, as no findings in the rabbit irritation study and the acute oral study. Because of animal welfare reasons the study is not necessary.

Currently no study to assess toxicity of FAT 93580/A TE on acute dermal exposure is available. However, the molecular weight of the substance is 367.3 - 645.6 g/mol, which indicates the substance being fairly large for dermal absorption. Further, water solubility of the test item at a temperature of 20 °C was determined to be < 0.1 mg/l which indicates the substance being highly hydrophobic. Hence, the dermal uptake for the substance is expected to be low. Further results of exposure to test animals from the acute toxicity studies via oral route indicated low toxicity potential and no classification was needed for acute toxicity or STOT SE. Taking into consideration the above arguments, no elevated toxicity other than already seen in acute oral toxicity studies is expected via the dermal route and safety for human health can be estimated using the principles of route to route extrapolation. Similarly, absence of systemic toxicity or mortality in skin irritation as well as sensitization studies with FAT 93580/A TE, further supports the conclusion that no additional adverse effects other than seen in acute oral toxicity studies are expected via dermal route. Hence, the conduct of acute toxicity study via dermal route for FAT 93580/A TE is considered to be scientifically not necessary.

Justification for classification or non-classification

Based on the LD50 value and exposure related observations from both the studies the acute oral median lethal dose (LD50) of the test item can be concluded to be greater than 2000 mg/kg body weight which can be classified as non-hazardous.