Registration Dossier

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Administrative data

Description of key information

rat, oral: LD50 > 300 < 2000mg/kg b.w. (BASF SE 2013, GLP, OECD423)
rat, dermal: LD50 > 5000mg/kg b.w. (BASF SE 2013, GLP, OECD 402)

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)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted Dec. 2001
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
adopted May 2008
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
adoopted Dec. 2002
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: app. 10 weeks
- Weight at study initiation: 172-191g
- Fasting period before study: 16h, water available ad lib.
- Housing: single in Makrolon type III cages
- Diet (e.g. ad libitum): VRF1(P) ad libitum; SDS Special Diets Services, 67122 Altrip, Germany
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 30-70%
- Air changes (per hr): app. 10
- Photoperiod (hrs dark / hrs light): 12h/12h
Route of administration:
oral: gavage
Vehicle:
olive oil
Remarks:
(high dose was administered undiluted)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.23mL/kg b.w.
Doses:
300, 2000mg/kg
No. of animals per sex per dose:
3 (high dose), 6 (low dose, incl. repeat experiment)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of application, at least once daily on workdays thereafter
- Frequency of weighing: shortly before administration, weekly thereafter (additionally on day of death, if found dead or sacrificed moribund)
- Necropsy of all animals performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
< 2 000 mg/kg bw
Based on:
test mat.
Mortality:
In the 2000 mg/kg test group two animals were found dead on study day 8 or 9 after administration. Due to the high weight loss, the remaining animal of this test group was sacrificed in a moribund state on study day 9. No mortality occurred in the 300 mg/kg test groups.
Clinical signs:
In the animals of the 2000 mg/kg bw test group, impaired general state, dyspnoea, piloerection, reduced feces, and exsiccosis were noted from study day 2 or 3 onwards. In the animal that was sacrificed moribund, poor general state and cachexia were noted on study day 9.

In the first 300 mg/kg bw test group impaired general state, dyspnoea and piloerection were observed in all animals from hour 2 until hour 5 after administration and persisted in one animal until study day 3. In another animal these findings were noted again on study day 2 and 3. No clinical signs were observed during clinical examination in the second 300 mg/kg administration group.
Body weight:
In the 2000 mg/kg bw test group high weight loss was noted during the post observation period until study day 9, when the surviving animal was sacrificed moribund (app. -19% in all animals).
The mean body weight of the surviving animals in the 300 mg/kg test groups increased within the normal range throughout the study period.
Gross pathology:
In the animals that died Peyer’s plaques in the small intestine (one animal) and swollen lymph nodes in region of the small intestine and red discoloration of the small intestine in the second animal. In the animal that was sacrificed moribund swollen lymph nodes in region of the small intestine and red discoloration of the small intestine were also observed.

There were no macroscopic pathological findings in the surviving animals sacrificed at the end of the observation period (300 mg/kg, 6 females).
Interpretation of results:
sligthly toxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted Feb. 1987
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
adopted May 2008
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
adopted August 1998
Qualifier:
according to guideline
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Wega GmbH, Sulzfeld, Germany
- Age at study initiation: males: app. 8 weeks, females: app. 12 weeks
- Weight at study initiation: on average: 227.6g (males), 203.4g ( females)
- Fasting period before study: no
- Housing: single in Makrolon type III cages
- Diet (e.g. ad libitum): VRF1(P) ad lib., SDS Special Diets Services, Altrip, Germany
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

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

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: app. 40cm² (= at least 10% of body surface)
- Type of wrap if used: air-permeable dressing (4 layers of absorbent gauze (Ph. Eur. supplied by Lohmann GmbH & Co., KG) and stretch bandage (Fixomull® Stretch (adhesive fleece) supplied by Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after removal of the dressing with warm water

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5.58mL/kg b.w.

Duration of exposure:
24h
Doses:
5000mg/kg
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: several times on the day of application, at least once daily on workdays thereafter
- Frequency of weighing: shortly before administration, weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: scoring of skin findings according to Draize (30-60min after removal of the dressing and several times until the end of the study)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality
Mortality:
No mortality occured
Clinical signs:
No systemic toxicity was observed in males or females.

In all male animals moderate erythema (grade 3) was noted on study day 2 and 3 and persisted in one animal until study day 8 and decreased in this animal to well defined erythema (grade 2) until study day 13 and very slight erythema (grade 1) on study day 14. Furthermore well-defined erythema (grade 2) was observed in one out of the five animals on study day 6 and 7 which decreased to very slight erythema on study day 8.
From study day 2 to study day 3 slight edema (grade 2) was observed in four animals. The fifth animal showed slight edema (grade 2) on day 2, which increased to edema grade 3 from day 3 to day 7, decreased to grade 2 again on day 8, and to grade 1 on study day 9. Incrustations were observed in all animals from study day 3 until study day 10, 13 or 14. Scaling was noticed from study day 3 until study day 14 in all male animals while severe scaling was noted in one of these animals on study day 9.

In all female animals moderate erythema (grade 3) was noted on study day 2 and 3 and persisted in three animals until study day 7 or 8. Furthermore well-defined erythema (grade 2) was observed in all females, varying either from study day 6 to 9, 8 to 13, 8 to 9 or only on study day 6 or 9. Erythema decreased in all females to very slight erythema (grade 1) and was noted on study day 7 and 10 or only on day 10 or 14. On study day 2 or 3 slight or moderate edema (grade 2 or 3) was observed in all females and persisted in four females until study day 7 or 8. Very slight edema (grade 1) was seen in three animals on study day 8 or on study days 9 and 10. Incrustations were observed from study day 2 until study day 10 or 14 in all females. Scaling was noticed from study day 3 until study day 13 or 14 in all female animals, while severe scaling was noted in one of these females on study day 9.
Body weight:
The mean body weight of the male animals increased within the normal range throughout the study period.
Mean body weight of the female animals stagnated during the first post-exposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range.
Gross pathology:
No abnormalities detected.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

In an acute oral toxicity study according to OECD423 and GLP (BASF SE 2012), fasted female Wistar rats were given a single oral dose of 2000mg/kg undiluted Reaction products of Fatty acids, tall-oil, compds. with oleylamine and Fatty acids, C18-unsatd., trimers, compds. with oleylamine or 300mg/kg of the test substance in olive oil by gavage. The animals were observerd for 14 days and necropsy was performed. Of the three high dose females, two animals died on days 7 and 8, the surviving animal was sacrificed moribund on day 9. Impaired general state, dyspnoea, piloerection, exsiccosis, reduced feces, and weight loss were observed in all animals of this group. Gross pathology revealed swollen lymph nodes and peyer's plaques in region of the small intestine and red discoloration of the small intestine. No mortality was observed in the two independent experiments using 300mg/kg. In the first experiment, impaired general state, dyspnoea, and piloerection were observed, while no clinical signs occured in the second experiment. The body weight increased in the expected range. Thus the oral LD50 value for this substance is greater than 300mg/kg b.w., but below 2000mg/kg b.w.

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 5000 mg/kg bw of undiluted Reaction products of Fatty acids, tall-oil, compds. with oleylamine and Fatty acids, C18-unsatd., trimers, compds. with oleylamine to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours (BASF SE 2013). No mortality and no systemic toxicity was observed during the for 14 days observation period. The mean body weight of the male animals increased within the normal range throughout the study period. Mean body weight of the female animals stagnated during the first postexposure observation week, probably due to the bandage procedure, but increased during the second week within the normal range. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. The following test item-related local effects were recorded during the course of the study:

o Very slight to moderate erythema (grade 1 to 3)

o Very slight to moderate edema (grade 1 to 3)

o Scaling and severe scaling

o Incrustations

Accordingly, the acute dermal median lethal dose (LD50) was determined to be > 5000 mg/kg b.w. in rats.

In accordance with column 2 of REACH Annex VIII, no acute inhalation toxicity study was conducted as two other routes are provided.

Justification for classification or non-classification

Based on the results of the available studies, the reaction mass of fatty acids, tall-oil, compds. with oleylamine and fatty acids, C18-unsatd., trimers, compds. with oleylamine classified as harmful after oral exposure, R22 according to 67/548/EEC and cat. 4 according to CLP/EU-GHS requirements. The test substance does not have to be classified for ist toxic potential after dermal exposure.