Fatty acids, tall-oil, reaction products with diethylenetriamine

Endpoint summary

Description of key information

In a GLP-compliant acute oral toxicity study according to OECD Guideline 423, no mortality occurred and no clinical signs were seen at the limit dose of 2000 mg/kg bw. Therefore, the oral LD50 was calculated to be greater than 2000 mg/kg bw in rats.

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:

Mar - Apr 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 17, 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

(from the competent authority) Landesanstalt für Umwelt Baden-Württemberg

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 0017319511
- Expiration date of the batch: December 18, 2018
- Purity: > 99 %
- Physical state / color: Solid, waxy / white to yellowish

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature
- Stability under test conditions: The homogeneity of the test item preparation during administration was ensured by stirring with a magnetic stirrer.
- Solubility and stability of the test substance in the solvent/vehicle: good homogeneity in corn oil Ph.Eur.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For better handling the test item was heated at approx. 50 °C. The test item preparation was prduced for each administration group shortly before administration with a spatula and by stirring with a magnetic stirrer. The test item preparation was administere lukewarm.

FORM AS APPLIED IN THE TEST (if different from that of starting material) : suspension

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI (Han) SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH; Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: animals of comparable weight (± 20 % of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing in fully air-conditioned rooms
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: At least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C ± 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Route of administration:

oral: gavage

Vehicle:

corn oil

Remarks:

Ph.Eur.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 40 g/100 mL
- Amount of vehicle (if gavage): 5.00 mL/kg bw
- Justification for choice of vehicle: Good homogeneity in corn oil Ph.Eur.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION (if unusual): For better handling the test item was heated at approx. 50 °C. The test item preparation was produced for each administration group shortly before administration with a spatula and by stirring with a magnetic stirrer. The test item preparation was administered lukewarm.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: By request of the sponsor a starting dose of 2000 mg/kg bw was chosen in the first step with 3 female animals. Because no mortality occurred, a further dose of 2000 mg/kg bw was administered to another group of 3 female animals in the second step.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter. A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes

Statistics:

Calculations were performed using Microsoft Excel 2010 and checked with a calculator.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occurred

Mortality:

No mortality occurred in both 2000 mg/kg bw test groups.

Clinical signs:

other: No clinical signs were observed during clinical examination in both 2000 mg/kg bw test groups.

Gross pathology:

There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females).

Table 1: Mortality

Dose [mg/kg bw]	2000	2000
Sex	Female	Female
Administration	1	2
No. of animals	3	3
Mortality (animals)	No mortality	No mortality

Table 2: Maximum incidence of clinical signs

Dose [mg/kg bw]	2000			2000
Sex	Female			Female
Administration	1			2
No. of animals	3			3
Animal No.	R 151	R 152	R 153	R 154	R 155	R 156
Abnormalities	-	-	-	-	-	-

Table 3: Body weights

Dose [mg/kg bw]	2000					2000
Administration	1					2
Animal No.	R 151	R 152	R 153	Mean weight	Standard deviation	R 154	R 155	R 156	Mean weight	Standard deviation
Body weight at study day [g]
0	178	176	168	174.0	5.29	179	173	169	173.7	5.03
7	200	193	183	192.0	8.54	200	189	191	193.3	5.86
14	215	195	189	199.7	13.61	207	198	207	204.0	5.20

Table 4: Gross pathology

Dose [mg/kg bw]	2000			2000
Administration	1			2
No. of animals	3			3
Animal No.	R 151	R 152	R 153	R 154	R 155	R 156
Macroscopic pathologic abnormalities	-	-	-	-	-	-

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test substance after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, a dose of 2000 mg/kg bw of the test item (preparations in corn oil Ph.Eur.) was administered by gavage to two test groups of three fasted Wistar rats each.

2000 mg/kg (both test groups):

- No mortality occurred

- No clinical signs were observed

- All animals gained weight in a normal range throughout the study period

- There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females)

The acute oral LD50 was calculated to be greater than 2000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

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

In an acute oral toxicity study performed according to the Acute Toxic Class Method, a dose of 2000 mg/kg bw of the test item (preparations in corn oil Ph.Eur.) was administered by gavage to two test groups of three fasted Wistar rats each.

2000 mg/kg (both test groups):

- No mortality occurred

- No clinical signs were observed

- All animals gained weight in a normal range throughout the study period

- There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period (6 females)

The acute oral LD50 was calculated to be greater than 2000 mg/kg bw in rats.

Justification for classification or non-classification

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

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. No mortality occurred at the limit dose of 2000 mg/kg bw. As a result, the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EC) No. 2017/776.