Amines, rosin

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 15 September 2015 to 15 October 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conclusive, performed to a valid guideline (OECD TG 423 adopted 17 December 2001) and was conducted under GLP conditions. No deviations from the test methods were noted.

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

Statement of GLP compliance signed by study director 18 December 2015

Test type:

acute toxic class 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:

- Name of test material (as cited in study report): Rosin Amine 90
- Physical state: transparent pale amber viscous liquid
- Lot/batch No.: 542700
- Expiration date of the lot/batch: 31 March 2016
- Radiochemical purity (if radiolabelling):
- Storage condition of test material: at room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Approximately 9-12 weeks
- Weight at study initiation: 165-203 g
- Fasting period before study: Overnight prior to dosing and until 3-4 hours after administration of the test substances
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV 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 outwith fasting period
- Water (e.g. ad libitum): Tap water provided ad libitum
- Acclimation period: At least 5 days before start of treatment under laboratory conditions

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

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.0202 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit test as specified by testing guideline

Doses:

2000 mg/kg (2.0202 mL/kg) body weight.
300 mg/kg (0.303 mL/kg) body weight.

No. of animals per sex per dose:

3 (stepwise treatment)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality/viability observations made twice daily, body weights recorded Days 1, 8 and 15 and at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs observations made at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, one animal was sacrificed for humane reasons on Day 8 (more than 20% body weight loss) and one animal was found dead on Day 10.
At 300 mg/kg, no mortality occurred.

Clinical signs:

other: At 2000 mg/kg, hunched posture, piloerection, hypotonia, uncoordinated movements, lean appearance and salivation were noted for the animals between Days 1 and 13. Additionally, the animals that died during the study showed lethargy, chromodacryorrhoea (sn

Gross pathology:

At 2000 mg/kg, abnormalities of the spleen (discolouration, pale), thymus (reduced in size), esophagus (contents: hemorrhagic/clotted blood), stomach (focus/foci, several, dark red) were found in the animals that died during the study. Additionally, it was noted that the animal sacrificed for humane reasons was emaciated.
Macroscopic post mortem examination of the surviving animals treated at 2000 mg/kg and the animals treated at 300 mg/kg, did not reveal any abnormalities.

Any other information on results incl. tables

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

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Remarks:

Iinformation Criteria used for interpretation of results: EU

Conclusions:

The oral LD50 value of Rosin Amine 90 in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.

Based on these results, according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), Rosin Amine 90 should be classified as Category 4 and should be labelled as H302: Harmful if swallowed.

Executive summary:

The study was carried out based on the guidelines described in: OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

Commission Regulation (EC) No 440/2008, B1 tris: "Acute Oral Toxicity, Acute Toxic Class Method" EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

JMAFF Guidelines (2000), including the most recent revisions.

Initially, Rosin Amine 90 was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure three additional groups of three females were dosed at 2000, 300 and 300 mg/kg body weight. The 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).

At 2000 mg/kg, one animal was sacrificed for humane reasons on Day 8 (more than 20% body weight loss) and one animal was found dead on Day 10. At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, hunched posture, piloerection, hypotonia, uncoordinated movements, lean appearance and salivation were noted for the animals between Days 1 and 13. Additionally, the animals that died during the study showed lethargy, chromodacryorrhoea (snout) and red staining of the mouth and nose. At 300 mg/kg, hunched posture was noted for all animals on Day 1.

At 2000 mg/kg, all animals showed body weight loss or reduced body weight gain between Days 1 and 8. The surviving animals showed normal body weight gain on Day 15 compared to Day 1, except for one animal which showed reduced body weight gain. At 300 mg/kg, the body weight gain shown by these animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

At 2000 mg/kg, abnormalities of the spleen (discolouration, pale), thymus (reduced in size), esophagus (contents: hemorrhagic/clotted blood), stomach (focus/foci, several, dark red) were found in the animals found dead. Additionally, it was noted that the animal sacrificed for humane reasons was emaciated. Macroscopic post mortem examination of the surviving animals treated at 2000 mg/kg and the animals treated at 300 mg/kg, did not reveal any abnormalities.

The oral LD50 value of Rosin Amine 90 in Wistar rats was established to be within the range of 300-2000 mg/kg body weight. According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 2000 mg/kg body weight.

Based on these results and according to the UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS) (2011) (including all amendments), Rosin Amine 90 should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route; - according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures (including all amendments), Rosin Amine 90 should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.