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Administrative data

Description of key information

Acute toxicity: 
Oral (OECD 401), rat: LD50 > 2000 mg/kg bw
Dermal (OECD 402), rat: 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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Institut für Versuchstierzucht, A-2325 Himberg
- Age at study initiation: approx. 8 weeks
- identification: labelling with felt-tipped pen on th tail and on the cage
- Weight at study initiation: mean 257 g (males), 165 g (females)
- Fasting period before study: Feed was withrawn the evening before application and was offered again about 3 hours after aplication.
- Housing: single caging in Makrolon type II cages (16.5x22x14 cm) with wire mesh lids and grid floors till 7 days p.a.
- Bedding material: granulated soft wood (agromed-Zechner), gamma-irridated with 10 kGy 60Co
- Diet (ad libitum): Altromin 1314 ff, gamma-irridated with 10 kGy 60Co; Random samples of the feed are analyzed for contaminants by Altromin, D-6937 Lage
- Water (ad libitum): Tap water, UV-irridated, offerd in Makrolon bottles with stainless steel canules
- Acclimation period: 11 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): average of 22
- Humidity (%): average of 55
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 1 male and 1 female
Main study: 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Behaviour, reactions and physical signs were observed 1, 10, 30 min, 1, 2, 4 and 6 hours p.a. and then at least once every day. Body weight was determined before administration, 7 days p.a. and 14 days p.a.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no unscheduled deaths during the study.
Clinical signs:
Ruffled fur was noted once in one male, all other animals appeard normal.
Body weight:
Body weight gain of the animals was inconspicous and comparable to untreated animals
Gross pathology:
No abnormal findngs found.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The available study data of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.
Executive summary:

In an acute oral toxicity study, 5 male and 5 female Sprague-Dawley rats were given a single oral dose of the product Sacocell 309 containing 30% of CAS 91081-22-0) at a dose of 2000 mg/kg. No mortality was noted and only a single animal showed discomfort by ruffled fur. There were no treatment related changes in body weight and gross pathology did not revealed any abnormal findings.Thus, the oral LD50 was determined to be > 2000 mg/kg in male and female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted according to OECD guideline and GLP, tested with the source substance CAS 65997-04-8. Based on the structural similarities and the fact that the target substance is an adduct of the source substance, this study is considered valid for read-across.
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage JANVIER (53940 Le Genest St Isle- France)
- Age at study initiation: Male: 7 weeks old. Females: 8 weeks old
- Weight at study initiation: Male: 229-250g. Females: 200-215
- Housing: Animals were individually housed for the 24 hrs treatments; animals were grouped in 5 for the rest of the study
- Diet (e.g. ad libitum): freely supplied (M20-SDS)
- Water (e.g. ad libitum): tap water from public distribution system
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes per hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs darkness ( 07.00 am/19.00pm)
Type of coverage:
semiocclusive
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of the dorsal areal of the trunk
- % coverage: 100%
- Type of wrap if used: semi occlusive dressing (porous gauze patches hydrophilic Codex of 8 layer Gazin from Lohmann&Rauscher held in contact with the skin by means of 50 mm wide hypoallergenic micropore adhesive tape from 3M)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the gauze dressing were removed and the treated areas were rinsed with dimethyl sulfoxide.
- Time after start of exposure: 24hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight (2 or 4 g of the test item was weighted and dimethyl sulfoxide was added to a 10 or 20 mL volumetric flask.
Duration of exposure:
24 hrs
Doses:
2000 mg/kg body weight

No. of animals per sex per dose:
5
Details on study design:
- Duration of observation period following administration: 14 days (or other?) 14 days
- Frequency of observations and weighing: Daily examinations were carried out to identify any behavioural or toxic effects on the physiological functions during 14 days following the administration of the test material. The animals were weighed on day D0, D2, D7 and D14.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality, no systemic clinical signs
Mortality:
No mortality
Clinical signs:
No systemic clinical signs related to the administration of the test item
Body weight:
The body weight gain remained normal throughout the study
Other findings:
The microscopic examination of the animals was conducted at the end of the study. The result did not reveal treatment-related changes.
Erythema and yellow coloration of the treated area were noted from 24 hrs post-dose in all animals and were totally reversible on D8.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal LD50 of the test item Rosin fumarated, CAS No. 65997-04-8 is higher than 2000 mg/kg body weight.
Executive summary:

The acute dermal toxicity of Rosin fumarated was evaluated using 5 male and 5 female Sprague Dawley rats. The fur was removed from the dorsal area of the trunk of the animals by clipping and a dose of 2000 mg/kg body weight was applied onto the 10% of the clear skin for 24 hrs. The treated area was covered by a semi-occlusive dressing consisting of a gauze patches hydrophilic, which was held in contact with the skin by means od 50 mm wide hypoallergenic micropore adhesive tape. After 24 hrs exposure, the gauze was removed and the treated area was rinsed with dimethyl sulfoxide. The animals were observed for 24 hrs. Signs of toxicity and behavioural effect were recorded daily, while weight gain was recorded at D0, D2, D7 and D14. No mortality occurred during the study. The results showed no signs of toxicity related to the administration of the test material. Erythema and yellow coloration of the treated area were noted from 24 hrs post-dose in all animals and were totally reversible on D8. No change in body weight was recorded and macroscopic examination did not show any treatment related changes. In conclusion, the LD50 of Rosin fumarated is higher than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Oral

The acute oral toxicity was investigated in a study performed in accordance with OECD 401, where rats were dosed with a solution containing 30% of resin acids and rosin acids, fumarated, compds. with triethanolamine (Hruby and Hofer, 1990).As no substance related clinical signs were noted and no mortality occurred, the LD50 was found to be >2000 mg/kg bw. 

The same result was also found for the analogue and hydrolysis product rosin, fumarated, which was tested in an acute oral toxicity study performed according to OECD 425 and GLP (Inveresk Research, 2002). 5 female Sprague-Dawley rats were given a single oral dose of Rosin, fumarated in maize oil at a dose of 2000 mg/kg.There were no treatment related clinical signs, necropsy findings or changes in body weight. The oral LD50 was determined to be > 2000 mg/kg in female rats.

In another acute oral toxicity study, performed according to OECD 401 and GLP, with rosin, fumarated, 5 male and 5 female Sprague-Dawley rats were given a single oral dose of 2000 mg/kg in 0.5% methylcellulose at a dose (Life Sciences Research, 1991b).Clinical signs of toxicity included staggered gait, piloerrection, ungroomed appearance, hunched posture, and diarrhoea; however, all animals normal by day 4. There were no treatment related changes in body weight. Gross pathology results showed two females with large mandibular lymph nodes. The oral LD50 was determined to be > 2000 mg/kg in male and female rats.

Thus, the available data on the test substance as well as the data of the analogue and possible hydrolysis product rosin, fumarated indicate a low oral toxicity with an LD50 of > 2000 mg/kg.

Inhalation

No studies on acute inhalation toxicity are available. However, no inhalation exposure is expected in view of the use of the substance (no aerosol formation) and the low vapour pressure

Dermal

Data on acute dermal toxicity by the analogue and hydrolysis product rosin, fumarated was used for assessment. The acute dermal toxicity of rosin fumarated was evaluated in accordance with GLP and OECD 402 and EU method B.3 using 5 male and 5 female Sprague Dawley rats (Phycher Bio Developpement, 2012). The fur was removed from the dorsal area of the trunk of the animals by clipping and a dose of 2000 mg/kg body weight was applied onto the 10% of the clear skin for 24 hrs. The treated area was covered by a semi-occlusive dressing consisting of a gauze patches hydrophilic, which was held in contact with the skin by means of 50 mm wide hypoallergenic micropore adhesive tape. After 24 hrs exposure, the gauze was removed and the treated area was rinsed with dimethyl sulfoxide. The animals were observed for 24 hrs. Signs of toxicity and behavioral effect were recorded daily, while weight gain was recorded at D0, D2, D7 and D14. No mortality occurred during the study and no signs of toxicity related to the administration of the test material were noted. No change in body weight was recorded and macroscopic examination did not show any treatment related changes. In conclusion, the LD50 of rosin, fumarated was higher than 2000 mg/kg in this study.

 Thus, the available data on the analogue and possible hydrolysis product rosin, fumarated indicate a low toxicity with an LD50 of > 2000 mg/kg, which could be also expected for resin acids and rosin acids, fumarated, compds. with triethanolamine.

 

 


Justification for selection of acute toxicity – oral endpoint
Reliable guideline studies.

Justification for selection of acute toxicity – dermal endpoint
Reliable guideline studies.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.