Amines, rosin

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 October-29 October 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Amines, rosin

EC Number:

263-139-8

EC Name:

Amines, rosin

Cas Number:

61790-47-4

Molecular formula:

C19H31N1

IUPAC Name:

1-[(1R,4aR,10aS)-1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl]methanamine; 1-[1,4a-dimethyl-7-(propan-2-yl)-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl]methanamine

Test material form:

liquid: viscous

Details on test material:

- Physical state: transparent pale amber viscous liquid
- Lot/batch No.: 542700
- Expiration date of the lot/batch: 31 March 2016
- Storage condition of test material: At room temperature

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: 542700
- Expiration date of the lot/batch: 31 March 2016
- Purity: not specified

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: Stable under the storage conditions until the expiry date

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: The test substance was dosed undiluted as delivered by the sponsor.
- No correction was made for the purity/composition of the test substance.
- An adjustment was made for the specific gravity of the test susbtance.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Approx. 10 weeks old
- Weight at study initiation: Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: None
- Housing: Individually housed in labeled Makrolon cages (MIII type, height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) provided ad libitum
- Water (e.g. ad libitum): Tap water provided ad libitum
- Acclimation period: At least 5 days before the start of the treatment under laboratory conditions.During the acclimatization period the animals were group housed in Makrolon cages (MIV type, height 18 cm).

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40 to 70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 5 x 7 cm. On the day before exposure this area on the back of each animal was clipped.
- % coverage: 10 of total body surface (approximately 25 cm^2 for males and 18 cm^2 females)
- Type of wrap if used: surgical gauze patch (Surgy 1D) successively covered with aluminium foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin cleaned of residual test substance using tap water.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution): 0.99 g/mL
- Constant volume or concentration used: yes
- For solids, paste formed: not applicable

Duration of exposure:

24 hours after which dressings were removed and the skin was cleaned of residual substance using tap water.

Doses:

2000 mg/kg (2.02 mL/kg) body weight

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 and weighing: Twice daily
- Necropsy of survivors performed:Yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: body weights observations were performed at Days 1 (pre-administration), 8 and 15 and at death (if sacrificed after Day 1)., clinical signs were monitored at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

In consultation with a veterinarian, one male and one female animal were sacrificed for humane
reasons on Day 6, due to severe irritation of the treated skin area. No further mortality occurred. For full table of results see attached document.

Clinical signs:

other: Flat posture, hunched posture and/or chromodacryorrhoea were noted for all animals between Days 1 and 3. Additionally, one animal showed hunched posture up to Day 8. General erythema, erythema maculate, scales, scabs, thickened areas, fissures, wounds a

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals. For full table of results see attached document.

Any other information on results incl. tables

Please see the 'Attached background material' section for the tables of results.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of the study, since there were no mortalities observed as a result of systemic toxicity caused by the test substance, the dermal LD50 value of Rosin Amine 90 in male and female Wistar rats was established to be more than 2000 mg/kg bw. According to GHS and EC Regulation No. 1272/2008, the test substance does not have to be classified and has no obligatory labelling requirements for acute dermal toxicity.

Executive summary:

This study was conducted to assess the systemic toxicity of the test substance, Rosin Amine 90, in a process carried out in accordance with the following guidelines; OECD No.402 (1987) "Acute Dermal Toxicity", Commission Regulation (EC) No 440/2008, B3: "Acute Toxicity (Dermal)", EPA, OPPTS 870.1200 (1998), "Acute Dermal Toxicity" and JMAFF Guidelines (2000), including the most recent revisions. The study was thought to provide a rational basis for risk assessment in humans, since the dermal route is a possible route of exposure during the manufacture, handling or use of the test substance.

Rosin Amine 90 was administered to five Wistar rats of each sex by a single dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

The main clinical signs observed for all animals from Day 1 -3 were flat posture, hunched posture and/or chromodacryorrhoea. Additionally, one animal showed hunched posture up to Day 8. During he observation period, general erythema, erythema maculate, scales, scabs, thickened areas, fissures, wounds and/or brown staining were noted in the treated skin-area of the animals. In addition, one animal had scabs on the left flank during the observation period. Two animals (one male and one female) were sacrificed for human reasons on Day 6, but there were no mortalities as a result of systemic toxicity caused by the test substance. The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity. There were no abnormalities found during the macroscopic post-mortem examination of the animals.

Since no mortality occurred due to systemic toxicity by the test substance, the dermal LD50 value of Rosin Amine 90 in male and female Wistar rats was established to be more than 2000 mg/kg body weight. Based on these results, Rosin Amine 90 does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments).