Fatty acids, C18-unsaturated, 1,6 Hexanediol Diester

Endpoint summary

Description of key information

Oral (similar to OECD 401), rat: LD50 > 15000 mg/kg bw (RA from source substance Ditridecyl adipate (CAS 16958 -92 -2))

Dermal (Federal Hazardous Substances Act Regulations (16 CFR 1500.40)), rabbit: LD50 > 5000 mg/kg bw (RA from source substance Ditridecyl adipate (CAS 16958 -92 -2))

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Basic data given. Report was limited, study was not GLP conform and purity of test substance was not given.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 300 g
- Fasting period before study: 18 h

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

15000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily
- Necropsy of survivors performed: no data

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Mortality:

no mortality observed

Clinical signs:

other: On the day of application all animals showed diarrhea. Over the course of the study numbers of animals with diarrhea declined (1 male and female on day 1, and two males each on day 2 to day 4). Thereafter, no diarrhea was observed until day 13 and day 14

Table 1: Overview of clinical symptoms observed in rats treated by single oral gavage with 15000 mg/kg bw of test item

number of rats with sign (male/female)

day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

diarrhea

5/5

1/1

2/0

2/0

2/0

1/0

1/0

lethargy

2/2

1/1

1/0

flaccid

1/0

body oily

5/5

5/5

5/5

ptosis

1/0

1/0

chromorhinorrhea

1/0

1/0

2/0

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Control animals:

no

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 15 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: source: CAS 16958-92-2

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

In a study similar to OECD 401 with the source substance Ditridecyl adipate (CAS 16958-92-2) no acute oral toxicity potential was observed (LD50 > 15000 mg/kg bw). As explained in the analogue justification, this result is considered to be valid also for the target substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2) study from an analogue source substance. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to analogue justification for further details). The information from this source 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 is sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, 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

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Basic data given. The test was performed on intact and abraded skin. Test substance purity not given.

Qualifier:

according to guideline

Guideline:

other: Federal Hazardous Substances Act Regulations (16 CFR 1500.40)

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.2 kg (mean)

Type of coverage:

semiocclusive

Vehicle:

not specified

Details on dermal exposure:

TEST SITE
- Area of exposure: abdomen, not further specified

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rabbits were cleansed
- Time after start of exposure: 24 h

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 intakt skin (uneven numbered animals)
5 abraded skin (even numbered animals)

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing carried out on day 0 and 14, Draize scores determined on day 1, observation for clinical signs daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight, skin reactions

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: Animals with intakt skin: Diarrhoea was seen for animal 1 at days 9 and 10 and for animals 3 at days 4 to 8. Animal 5 had a bloated abdomen on day 13 and 14. Animals with abraded skin: Diarrhoea was seen for animal 2 at day 5 and for animal 4 on days 5 to

Gross pathology:

no data

Other findings:

- Other observations:
Erythema (grade 1 or 2) was found in 9/10 animals, whereas edema (grade 1 or 2) was only observed in 3 animals.

Table1: body weight (kg)
rabbit	Day 0	Day 14
1	2	1.8
2	2.4	2.3
3	2.2	2
4	2.2	2
5	2.2	2.2
6	2.2	2.4
7	2.5	2.6
8	2.3	2.5
9	1.9	2.1
10	2.1	2

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Reference 2

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:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: source: CAS 16958-92-2

Interpretation of results:

other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008

Conclusions:

In a study according to Federal Hazardous Substances Act Regulations (16 CFR 1500.40) with the source substance Ditridecyl adipate (CAS 16958-92-2) no acute dermal toxicity potential was observed (LD50 > 5000 mg/kg bw). As explained in the analogue justification, this result is considered to be valid also for the target substance.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate, reliable (Klimisch score 2) study from an analogue source substance. Read-across is justified based on common functional group(s), common precursors/breakdown products and similarities in PC/ECO/TOX properties (refer to analogue justification for further details). The information from this source 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 is sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No. 1907/2006.

Additional information

Justification for read-across

There are no data for acute toxicity available for Fatty acids, C18-unsaturated, 1,6 Hexanediol Diester (EC 947-912-3). To fulfil the standard data requirements defined in Regulation (EC) No. 1907/2006, Annex VII-VIII, 8.5, read-across from an appropriate substance is conducted in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. According to 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) “to avoid the need to test every substance for every endpoint”.

For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substances are the basis of read-across. A detailed justification for the analogue read- across approach is provided in the technical dossier (see IUCLID Section 13).

As no experimental data are available on acute toxicity of Fatty acids, C18 -unsaturated, 1,6 Hexanediol Diester (EC 947-912-3), read-across of reliable data on the analogue substance Ditridecyl adipate (CAS 16958-92-2) was conducted.

Acute oral toxicity

CAS 16958-92-2

The acute oral toxicity of Ditridecyl adipate (CAS 16958-92-2) was assessed in a study according to OECD 401 (Exxon, 1978a, key). 5 female and 5 male rats received a dose of 15000 mg/kg bw via oral gavage. No mortality occured. Clinical signs were observed in all animals mainly in form of diarrhea. The number of animals affected declined during the observation time. Other symptoms were lethargy, flabbiness, oily body, ptosis and chromorhinorrhea, which were reversible, except of the chromorhinorrhea, which was observed on the last day of observation (no information given on whether it persisted or not). Therefore, the LD50 value was selected to be exceeding 15000 mg/kg bw in this study.

Acute dermal toxicity

CAS 16958-92-2

The acute dermal toxicity of Ditridecyl adipate (CAS 16958-92-2) was investigated in New Zealand White rabbits at a limit dose of 5000 mg/kg bw according to the Federal Hazardous Substances Act Regulations (16 CFR 1500.40) (Exxon, 1978b, key). The test substance at a limit dose of 5000 mg/kg bw was applied to the intact and abraded skin of 5 animals, respectively, under semi-occlusive conditions for a period of 24 h. No mortalities and no effects on the mean body weights were observed up to the end of the study. Diarrhoea occurred in 2/5 animals with intact skin and 2/5 animals with abraded skin during the 14-day observation period. A bloated abdomen was observed in a single animal (intact skin) on Day 13 and 14 of the study. Further clinical signs included emaciation in 2 animals (abraded skin) as well as lethargy in one of these animals. After exposure, the test substance was removed and skin irritation was assessed according to the Draize scoring system. Erythema (grade 1 or 2) was found in 9/10 animals, whereas edema (grade 1 or 2) was only observed in 3 animals. Based on these results, the dermal LD50 value for rabbits was found to be greater than 5000 mg/kg bw.

 

Reliable data available for the read-across analogue substance Ditridecyl adipate (CAS 16958-92-2) indicate no acute toxicity following the oral and dermal route as the defined LD50 values exceeds the limit value and no adverse effects at the applied dose have been observed. Thus, Fatty acids, C18-unsaturated, 1,6 Hexanediol Diester (EC 947-912-3) is not considered as hazardous after acute oral and dermal exposure.

Justification for classification or non-classification

Based on the analogue read-across approach, the available data on acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.