Fatty acids, C18-unsatd., dimers, compds. with coco alkylamines

Endpoint summary

Description of key information

rat, oral: LD50 > 2000mg/kg b.w. (BASF SE 2012, GLP, OECD423)
rat, dermal: LD50 > 5000mg/kg b.w. (BASF SE 2012, 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: 175.7 - 203.7g
- 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:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.22mL/kg b.w.

DOSAGE PREPARATION (if unusual): the test item was heated at 70°C for app. 1h for better handling, and administered luke warm

Doses:

2000

No. of animals per sex per dose:

6 (in two experiments with 3 animals each)

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
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality occured

Mortality:

No mortality occured

Clinical signs:

other: In the first experiment, impaired general state and dyspnoe occured in all animals for up to 4h during the first day. Salivation right after application and piloerection (2h - 4h after application) was observed in two animals. The second test group showed

Gross pathology:

No abnormalities observed.

Interpretation of results:

practically nontoxic

Remarks:

Migrated information

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

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 229.8g (males), 213.0g (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): 5.55mL/kg b.w.
- For better handling the test item was heated at 60°C for approx. 1 hour. The test item was administered lukewarm.

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: clinical signs, body weight, 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:

other: No systemic toxicity was observed in males or females. Well-defined erythema (grade 2) and very slight edema (grade 1) were noted in all male animals from study day 1 until study day 3 after application. Furthermore scaling was observed in 3 male animals

Gross pathology:

No abnormalities detected.

Tabel 1

Nature and duration of local clinical signs(males)
Animal No.:	R 902	R 903	R 904	R 905	R 906
Erythema grade 2:	d1 - d3	d1 - d3	d1 - d3	d1 - d3	d1 - d3
Edema grade 1:	d1 - d3	d1 - d3	d1 - d3	d1 - d3	d1 - d3
Scaling:	d3 - d14	d3 - d8	d3 - d14	d3 - d10	d3 - d14
Incrustations:	d3 - d14	d7 - d8	d7 - d14	d7 - d10	d8 - d14

Table 2

Nature and duration of local clinical signs(females)
Animal No.:	R 907	R 908	R 909	R 910	R 911
Erythema grade 1:	d6 - d9	d6 - d9	d6 - d9	d6 - d9	d6 - d8
Erythema grade 2:	d1 - d3	d1 - d3	d1 - d3	d2 - d3	d2 - d3
Erythema grade 3:	-	-	-	d1	d1
Scaling:	d3 - d9	d3 - d9	d3 - d9	d3 - d10	d3 - d10
Incrustations:	d7 - d14	d6 - d14	d2 - d14	d2 - d9	-

d: day

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), 6 female fasted Wistar rats (3 each in two independent experiments) were given a single oral dose of 2000mg/kg undiluted fatty acids, C18-unsatd., dimers, compds. with coco alkylamines by gavage. The animals were observerd for 14 days and necropsy was performed. No mortality occured. Clinical signs, i.e., bad general state, dyspnoe, salivation, and piloerection, were observed for up to four hours on the first day during the first experiment only. The expected body weight gain had been observed in the course of the study. No abnormalities were noted at necropsy of animals sacrificed at the end of the study. Thus the oral LD50 value for this substance is greater than 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 Fatty acids, C18- unsatd., dimers, compds. with coco alkylamines to the clipped skin

(dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours (BASF SE 2012). 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 edema (grade 1)

o 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, fatty acids, C18-unsatd., dimers, compds. with coco alkylamines is not required to be classified for its acute toxicity potential according to 67/548/EEC and CLP/EU-GHS requirements.