Registration Dossier

Administrative data

Description of key information

Oral: LD50 (rat, m/f) > 5000 mg/kg bw (OECD 401, GLP, read-across from structurally similar substances)
Dermal: LD50 (rat, m/f) > 2000 mg/kg bw (OECD 402, GLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2 due to read-across) studies from reference substances with similar structure and intrinsic properties. Read-across is justified based on common functional groups, common precursors/breakdown products and similarities in physicochemical and (eco)toxicological properties> (refer to endpoint discussion for further details).
Taken together, the information from these independent sources is consistent and provides sufficient weight of evidence for hazard assessment leading to an endpoint conclusion in accordance with Annex XI, 1.2, of Regulation (EC) No 1907/2006. Therefore, the available information as a whole is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5.1, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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:
experimental study
Adequacy of study:
key study
Study period:
14 Nov - 05 Dec 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-Guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
The Department of Health of the Government of the United Kingdom, UK
Test type:
standard acute method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
other: RccHan™:WIST
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 235-273 g (males); 200-216 g (females)
- Housing: The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 h exposure period and in groups of up to four, by sex, for the remainder of the study.
- Diet: 2014C Teklad Global Rodent diet (Harlan Laboratories UK Ltd., Oxon, UK), ad libitum
- Water: mains drinking water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12 / 12
Type of coverage:
semiocclusive
Vehicle:
other: unchanged (no vehicle), moistened with arachis oil BP
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks (clipped free of hair)
- % coverage: approx. 10%
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied: For the purpose of the study the test item was weighed out according to each animal’s individual bodyweight and moistened with arachis oil BP prior to application.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Procedure: Initially, two animals (one male and one female) were given a single, 24-hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Based on the results of theinitial test, a further group of eight animals (four males and four females) was similarly treated.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days. Individual bodyweights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy (external examination and opening of the abdominal and thoracic cavities; the appearance of any macroscopic abnormalities was recorded; no tissues were retained), dermal reactions

DERMAL REACTIONS
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.



Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systemic toxicity.
Body weight:
Animals showed expected gains in bodyweight over the study period except for one female which showed bodyweight loss during the first week (ca. -7%) but expected gain in bodyweight during the second week.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
- Dermal reactions: Very slight erythema was noted at the test sites of eight animals (Table 1). Small superficial scattered scabs were also noted at the test sites of three females. There were no signs of dermal irritation noted in two males.

Table 1. Individual dermal reactions

Animal number

Observation

Effects noted after initiation of exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males

1

Erythema

0

1

1

1

1

0

0

0

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3

Erythema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

4

Erythema

0

1

0

0

0

0

0

0

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

Erythema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Females

1

Erythema

0

1

1

1

1

1

1

1

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

Other

0

0

Ss

Ss

Ss

Ss

Ss

Ss

Ss

Ss

0

0

0

0

2

Erythema

0

1

1

0

0

0

0

x

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

x

0

0

0

0

0

0

 

Other

0

Ss

Ss

0

0

0

0

x

0

0

0

0

0

0

3

Erythema

0

1

1

0

0

0

0

x

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

x

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

x

0

0

0

0

0

0

4

Erythema

0

1

1

0

0

0

0

x

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

x

0

0

0

0

0

0

 

Other

0

0

0

0

0

0

0

x

0

0

0

0

0

0

5

Erythema

0

1

1

0

0

0

0

x

0

0

0

0

0

0

 

Edema

0

0

0

0

0

0

0

x

0

0

0

0

0

0

 

Other

0

Ss

Ss

0

0

0

0

x

0

0

0

0

0

0

 

0 = No reactions

1 = Very slight erythema

Ss = Small superficial scattered scabs

x = Due to technician error observation not performed

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5.3, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are no data available on the acute oral toxicity of Fatty acids, C18-unsaturated, trimers, hydrogenated. In order to fulfil the standard information requirements set out in Annex VII, Section 8.5.1, in accordance with Annex XI, Section 1.5 of Regulation (EC) No 1907/2006, read-across from structurally similar substances is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) and Fatty acids, C18-unsatd., dimers, hydrogenated (CAS 68783-41-5) are selected as reference substances for assessment of the acute oral toxicity.

The read-across is based on structural similarity as a result of common origin and production process line. Shortly, the source and target substances are derived from catalytically di- and trimerised long-chain fatty acids; dimers and trimers are separated by distillation and unsaturated alkyl chains are hydrogenated as specifically required. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Overview of acute toxicity

 

Target substance (a)

Source substance 1 (b)

Source substance 2

CAS No.

 1373883-45-4

61788-89-4

68783-41-5

Chemical name

Fatty acids, C18-unsaturated, trimers, hydrogenated

Fatty acids, C18-unsatd., dimers

Fatty acids, C18-unsatd., dimers, hydrogenated

Acute toxicity: oral

WoE:

RA: CAS 61788-89-4

RA: CAS 68783-41-5

Experimental result:

LD50 (rat, m/f) > 5000 mg/kg bw

Experimental result:

LD50 (rat, m/f) > 5000 mg/kg bw

Acute toxicity: inhalation

Waiving

--

--

Acute toxicity: dermal

Experimental result:

LD50 (rat, m/f) > 2000 mg/kg bw

--

--

(a) The substance subject to the REACh Phase-in registration deadline of 31 May 2013 is indicated in bold font. Only for this substance a full set of experimental results and/or read-across is given.

(b) Reference (read-across) substances are indicated in normal font. Lack of data for a given endpoint is indicated by “--“.

 

Acute toxicity: oral

CAS 61788-89-4, CAS 68783-41-5

Fatty acids, C18-unsatd., dimers and Fatty acids, C18-unsatd., dimers, hydrogenated were tested for acute oral toxicity in rats in GLP-compliant studies conducted according to OECD guideline 401 and EU Method B.1, respectively (Thouin, 1986; Reijnders, 1988). In each study, one group of 5 male and 5 female rats was given a single oral dose of the respective test material at 5000 mg/kg bw by gavage. In both studies, no mortalities occurred and no signs of systemic toxicity were observed up to the end of the observation period (14 days). Likewise, no effects on body weight (change) and no test substance-related gross abnormalities were seen at macroscopic examination.

Based on the results of these studies, the oral LD50 of both Fatty acids, C18-unsatd., dimers and Fatty acids, C18-unsatd., dimers, hydrogenated in male and female rats was greater than 5000 mg/kg bw.

Acute toxicity: dermal

The acute dermal toxicity of Fatty acids, C18-unsaturated, trimers, hydrogenated was assessed in rats in a GLP-compliant study carried out according to OECD guideline 402 (Bradshaw, 2013). Initially, two animals (one per sex) were given a single, 24-hour, semi-occluded dermal application of the test item to the intact skin at a dose level of 2000 mg/kg bw. Based on the results of the initial test, a further group of 8 rats (4 per sex) was similarly treated.

No mortality occurred and no signs of systemic toxicity were observed up to the end of the 14-day observation period. Animals showed expected body weight gain, except for one female which showed bodyweight loss during the first week (ca. -7%) but expected gain in bodyweight during the second week. No abnormalities were observed at necropsy.

There were no signs of dermal irritation in 2 animals (males). Skin reactions were limited to very slight erythema (Draize score 1) at the test sites of 8 animals, without any signs of edema. Very slight erythema was seen in 2 males only on Day 2 and in another male on Days 2-5. In females, very slight erythema was noted in 4 animals on Days 2 and 3 and in one animal on Days 2-8. Small superficial scattered scabs were also noted at the test sites of 3 females (in two animals on Days 2-3 and in one animal on Days 3-10).

The maximum mean erythema scores from 3 consecutive readings was 1 in 2/10 animals, 0.7 in in 4/10 animals, 0.3 in 2/10 animals and 0 in 2/10 animals. Therefore, the substance can be considered to be not irritating to the skin.

Based on the study results the dermal LD50 in male and female rats is > 2000 mg/kg bw and the substance is thus considered to be not acutely toxic by the dermal route.

Inhalation

No relevant information available.

In accordance with Column 2 of Annex VIII, Section 8.5.2 of Regulation (EC) No 1907/2006, testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols , particles or droplets of inhalable size.

The substance is a viscous liquid with low vapour pressure and it is not intended for use in spraying/brushing processes. Therefore, human exposure to vapours, aerosols, particles or droplets of inhalable size is unlikely and testing by the inhalation route is not appropriate.

Conclusions for acute toxicity

The substance Fatty acids, C18-unsaturated, trimers, hydrogenated has been tested for acute dermal toxicity resulting in a dermal LD50 > 2000 mg/kg bw and no toxicologically relevant signs of systemic or local (dermal) effects.

There is no information available on acute oral toxicity. Therefore, in order to fulfil the standard information requirements set out in Annex VII, Section 8.5.1, in accordance with Annex XI, Section 1.5 of Regulation (EC) No 1907/2006, read-across from structurally similar substances is conducted.

Acute oral toxicity studies with Fatty acids, C18-unsatd., dimers (CAS 61788-89-4) and Fatty acids, C18-unsatd., dimers, hydrogenated (CAS 68783-41-5) resulted in oral LD50 values > 5000 mg/kg bw/day and no toxicologically relevant effects.

Based on the available data, the substance Fatty acids, C18-unsaturated, trimers, hydrogenated is considered to be not toxic by the oral and dermal routes.

Human exposure to vapours, aerosols, particles or droplets of inhalable size is unlikely as anticipated from the physicochemical properties (viscous liquid with low vapour pressure) and identified uses of the substance (no uses involving spraying/brushing processes).


Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from structural analogues. All available studies are equally adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
There is only one study available.

Justification for classification or non-classification

Based on substance specific data and read-across from structurally similar substances following an analogue approach, the available data on the acute oral and dermal toxicity of the substance do not meet the classification criteria according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Data on acute toxicity by inhalation are lacking.