Registration Dossier

Administrative data

Description of key information

Acute toxicity:
- Oral (OECD 401, GLP): LD50 >2000 mg/kg bw
- Dermal (OECD 402, GLP): LD50 >2000 mg/kg bw

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:
9 Oct - 6 Nov 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
In compliance with GLP and according to OECD guideline 420
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd.
- Age at study initiation: 8 to 12 weeks
- Fasting period before study: food removed overnight prior to dosingreturned three to four hours after dosing
- Housing: in groups up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (e.g. ad libitum): Rodent 2014C Teklad Global Certified Diet (Harlan Laboratories) ad libitum
- Water (e.g. ad libitum): ad libitium
- Acclimation period: at least 5 days
- Other: females were nulliparous and non-pregnant
- Other: bodyweight variation did not exceed appr 20% of the bodyweight of the initially dosed animal

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Justification for choice of vehicle: Test item did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: based on available information on toxicity of the test item
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 (females)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: morbidity/mortality: twice daily, early and late, during normal working days, once daily at weekends. Clinical observations half an hour and 1,2, and 4 hours after dosing, then daily for 14 days. Individual bodyweights recorded on day 0 (prior to dosing), day 7, and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: no
Statistics:
not relevant
Preliminary study:
Prior to the main test, a sighting test was performed in which 1 female rat was dosed 2000 mg/kg bw). Based on the absence of mortality, 4 additional animals were dosed with 2000 mg/kg bw.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
No signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the observation period.
Gross pathology:
No abnomalities were noted at necropsy.
Interpretation of results:
other: Not classified
Remarks:
Based on CLP criteria
Conclusions:
In an acute oral toxicity study which was performed according to guideline OECD420 (fixed-dose procedure) and under GLP conditions, the acute oral toxicity potential of Standolized Soybean Oil was investigated. The acute oral median lethal dose (LD50) of test item in the female Wistar strain rat was observed to be greater than 2000 mg/kg bw, under the conditions of this study. The substance therefore does not need to be classified according to the classification criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.
Executive summary:

In an acute oral toxicity study which was performed according to guideline OECD420 (fixed-dose procedure) and under GLP conditions, the acute oral toxicity potential of Standolized Soybean Oil was investigated. Following a sighting test at a dose level of 2000mg/kg bw, an additional four fasted female animals were administered a single oral dose of Standolized Soybean Oil as a solution in arachis oil BP, at a dose level of 2000 mg/kg bw. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

No mortality was noted and no signs of systemic toxicity were observed. Furthermore, no abnormalities were noted at necropsy. The oral LD50 of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw, under the conditions of this study. The substance therefore does not need to be classified according to the classification criteria outlined in Annex VI of 67/548/EEC and Annex I of 1272/2008/EC.

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:
other justification
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 February 2010 - 24 February 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study has been performed according to OECD and EC guidlines and according to GLP principles. A reliability of 2 is assigned in accordance with the ECHA Practical guide #6 on the reporting of read-across in IUCLID, due to the read-across purpose.
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 12 weeks old) were selected
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No
Housing: Individually housed in labeled Macrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Woody-Clean type 3/4, Tecnilab-BMI BV, Someren, The Netherlands) and paper as cage-enrichment (Enviro-dri, Tecnilab-BMI BV, Someren, The Netherlands).
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): Free access to tap water.
- Acclimation period: The acclimatization period was at least 5 days before the start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.

Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): : 20.0 - 22.0ºC
- Humidity (%): 38 - 56%
Temporary deviations from the minimum level of relative humidity occurred. Laboratory historical data do not indicate an effect of the deviations.
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 10 February 2010 To: 24 February 2010
Type of coverage:
occlusive
Vehicle:
corn oil
Remarks:
specific gravity 0.92
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
* Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours
Doses:
2000 mg/kg (10 mL/kg) body weight
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

Dose level (volume): 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle and the test substance.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded.
- Necropsy of survivors performed: yes
- Other examinations performed: none.
Statistics:
None
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, hunched posture and/or piloerection were noted in two males and one female on Day 2. Chromodacryorrhoea was observed in one male on Days 1 and 2.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
The incidence of slight body weight loss of animal no. 5 between Days 1 and 8 was considered not indicative of toxicity, based on the absence of any corroborative findings in this animal and since other animals showed normal weight gain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals
Interpretation of results:
other: Not classified
Remarks:
Based on CLP criteria
Conclusions:
The dermal LD50 value of Standolized linseed oil in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Standolized linseed oil does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the
-Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
-Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See attached justification
Reason / purpose:
read-across source
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Lethargy, hunched posture and/or piloerection were noted in two males and one female on Day 2. Chromodacryorrhoea was observed in one male on Days 1 and 2.
Body weight:
The mean body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
The incidence of slight body weight loss of animal no. 5 between Days 1 and 8 was considered not indicative of toxicity, based on the absence of any corroborative findings in this animal and since other animals showed normal weight gain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals
Interpretation of results:
other: Not classified
Remarks:
Based on CLP criteria
Conclusions:
The dermal LD50 value of Standolized linseed oil in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Standolized linseed oil does not have to be classified and has no obligatory labeling requirement for acute dermal toxicity according to the
-Globally Harmonized System of Classification and Labeling of Chemicals (GHS) of the United Nations (2007),
-Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

The results of Standolized Linseed Oil (SLO) can be read across to Standolized Soybean Oil (SSO) as SLO and SSO share similar structures and reactivity, based on the fatty acids composition of the raw material oils. Due to higher level of polyunsaturated fatty acid chains, SLO presents the worst case scenario in terms of toxicology. (see read across document for further details)

Acute oral toxicity studies are available for both SSO and SLO, which were performed in accordance with OECD Guideline 420 and 401, respectively. In the study with SSO, which was a fixed dose procedure, an LD50 value of >2000 mg/kg bw was observed. In the standard acute study which was performed with read across substance SLO, an LD50 of 4897 mg/kg bw was observed.

One acute dermal toxicity study with read across substance SLO is available which was performed in accordance with OECD Guideline 402 and under GLP conditions. The observed LD50 value was >2000 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
This study was selected as it is the only available oral acute toxicity study with Standolized Soybean Oil

Justification for selection of acute toxicity – inhalation endpoint
This waiver was selected for the endpoint conclusion as data for two other exposure routes is available.

Justification for selection of acute toxicity – dermal endpoint
This study was selected as it is the only available dermal acute toxicity study.

Justification for classification or non-classification

Based on the available information for acute toxicity, Standolized Soybean Oil does not need to be classified for this endpoint according to the criteria outlined in Annex I of CLP (1272/2008/EC) and Annex VI of DSD (67/548/EEC).