Addition reaction products of conjugated sunflower-oil fatty acids and tall-oil fatty acids with maleic anhydride

Endpoint summary

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: Well documented and reported study fully adequate for assessment. The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a recognized contract research organization.

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(17th Dec. 2001)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(30th May 2008)

Deviations:

no

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: CRL:(WI) rats
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Age at study initiation: adult rats, 8 weeks old
- Weight at study initiation: 192 – 207 g
- Fasting period before study: the night before treatment (water ad libitum)
- Housing: 3 animals / cage (Type II polypropylene/polycarbonate)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (+/- 3)
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg b.w.

MAXIMUM DOSE VOLUME APPLIED: ca. 2 ml

DOSAGE PREPARATION: The test material mixed with the vehicle was warmed up on a water bath to 50 ºC for approximately 10 minutes thus facilitating preparation of a suitable dose formulation. Pending administration to the animals, the dose formulation was stirred on a magnetic stirrer at room temperature and was protected from light.

Doses:

2000 mg/kg b.w.

No. of animals per sex per dose:

2 x 3 female rats /2000 mg/kg b.w. (incl. the confirmatory group)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of clinical observations: 30 min., 1, 2, 3, 4, 6 h after administration, daily for 14 days
weighing: day before treatment (day -1), day of treatment prior to dosing (day 0) and than weekly
- Necropsy of all animals performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no deaths

Mortality:

no mortality

Clinical signs:

other: Treatment with WS400104 at the dose of 2000 mg/kg bw caused transient decreased activity, hunched back and incoordination in all of six animals on the day of treatment. All animals recovered on Day 1.

Gross pathology:

No macroscopic observed effects

Table 1: CLINICAL OBSERVATIONS:DOSE: 2000mg/kg b.w., Treatment on Day 0

CageNo.	Animal Number	Observations	Observationdays
			0						1	2	3	4	5	6-14
			30'	1h	2h	3h	4h	6h
1	1176	SymptomFree	-	-	-	-	-	-	+	+	+	+	+	+
		Activitydecreased	1	1	1	1	1	1	-	-	-	-	-	-
		Hunchedback	-	+	+	+	-	-	-	-	-	-	-	-
		Incoordination	1	1	1	1	1	-	-	-	-	-	-	-
	1177	SymptomFree	-	-	-	-	-	-	+	+	+	+	+	+
		Activitydecreased	1	1	1	1	1	1	-	-	-	-	-	-
		Hunchedback	-	+	+	+	-	-	-	-	-	-	-	-
		Incoordination	1	1	1	1	1	-	-	-	-	-	-	-
	1178	SymptomFree	-	-	-	-	-	-	+	+	+	+	+	+
		Activitydecreased	1	1	1	1	1	1	-	-	-	-	-	-
		Hunchedback	-	+	+	+	+	+	-	-	-	-	-	-
		Incoordination	1	1	1	1	1	-	-	-	-	-	-	-
2	1179	SymptomFree	+	-	-	-	-	-	+	+	+	+	+	+
		Activitydecreased	-	-	1	1	1	1	-	-	-	-	-	-
		Hunchedback	-	-	+	+	-	-	-	-	-	-	-	-
		Incoordination	-	1	1	1	1	-	-	-	-	-	-	-
	1180	SymptomFree	+	-	-	-	-	+	+	+	+	+	+	+
		Activitydecreased	-	-	1	1	1	-	-	-	-	-	-	-
		Hunchedback	-	-	+	+	-	-	-	-	-	-	-	-
		Incoordination	-	1	1	1	1	-	-	-	-	-	-	-
	1181	SymptomFree	+	-	-	-	-	+	+	+	+	+	+	+
		Activitydecreased	-	-	1	1	1	-	-	-	-	-	-	-
		Hunchedback	-	-	+	+	-	-	-	-	-	-	-	-
		Incoordination	-	1	1	1	1	-	-	-	-	-	-	-

Interpretation of results:

other: not acutely toxic

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item WS400104 was found to be above 2000 mg/kg bw in female CRL:(WI) rats.
According to the Globally Harmonised System (GHS) (UNITED NATIONS 2005 and more recent revisions) and according to Regulation (EC) No 1272/2008 WS400104 should be ranked as "Unclassified" for acute oral exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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 the acute oral toxicity study no death occured at the highest recommended dose of 2000 mg/kg.

Justification for classification or non-classification

In the acute oral toxicity study, all animals survived the dose of 2000 mg/kg. Therefore, classification of WS400104 for acute oral toxicity is not required [REGULATION (EC) 1272/2008].

 

Non-classification of WS400104 by the dermal route was reasonable, because of the absence of effects indicative of relevant systemic toxicity (apart from the sensitization response) and local irritation in all available in vivo toxicity studies with WS400104 and the systemic exposure probably being higher by the oral than by the dermal administration route.

 

Non-classification of WS400104 by the inhalation route was justified, because WS400104 has a very low vapour pressure and is a highly viscous liquid, making the inhalation exposure of humans to vapour or a droplet aerosol unlikely