Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids

Endpoint summary

Description of key information

There is no data available for the acute toxicity of Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9). In order to fulfill the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from a structurally related substance was conducted.

The substance Dipentaerythritol hexaesters of nC5/iC9 consists of dipentaerythritol hexaesters with fatty acids C5 and C9 iso and it is considered to be similar to the target substance, on the basis of the structural and similar properties and/or activties.

The available acute toxicity study (oral route) for the source substance (GLP study, OECD 423 method, result LD50 > 2000 mg/kg bw) is used to predict the same behaviour for the target substance Dipentaerythritol hexaesters of 3,5,5 -trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9).

The available acute toxicity study (dermal route) for the source substance (GLP study, Annex V Directive 67/548/EEC guideline, result LD50 > 2000 mg/kg bw) is used to predict the same behaviour for the target substance Dipentaerythritol hexaesters of 3,5,5 -trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9).

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:

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

Adequacy of study:

key study

Justification for type of information:

There is no data available for the acute toxicity of Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9). In order to fulfill the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was 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 substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

The substance Dipentaerythritol hexaesters with fatty acids C5 and C9 iso is considered to be similar to the target substance, on the basis of the structural and similar properties and/or activities. The available acute toxicity study (oral route) for the source substance is used to predict the same endpoint for the target substance Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9)
A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 according to experimental results

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

No mortality occurred during the study period.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Body weight:

No effect on body weight was noted (see Table 1).

Gross pathology:

Necropsy revealed no substance-related findings.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute toxicity (oral route) study with source substance Dipentaerythritol wiht fatty acids C5 and C9iso (OECD 423) showed no mortality and no clinical sings of toxicity up to the end of the 14-day observation period. The study showed a LD50 > 2000 mgkg bw (for male/female) and no classification as per CLP was applicable to the test item for this hazard.

Based on the results from the structurally related source substance, it can be concluded that the target substance Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids will not exhibit acute toxicity effects by oral route.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 Dec - 23 Dec 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The Department of Health of the Government of the United Kingdom, UK

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley CD (Crl:CD® (SD) IGS BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Ltd, Margate, Kent, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 209-229 g (males) and 204-235 g (females)
- Fasting period before study: animals were fasted overnight prior to administration.
- Housing: animals were housed in groups of up to 3 per cage per sex in solid-floor polypropylene cages furnished with woodflakes.
- Diet: Rat and Mouse Expanded Diet No. 1 (Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-21
- Humidity (%): 37-67
- Air changes (per hr): at least 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.06 mL/kg bw

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: according to the author(s), the information available suggested a starting dose of 2000 mg/kg bw.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 min, 1, 2 and 4 h after dosing and subsequently daily for 14 days and individual body weights were determined prior to dosing and 7 and 14 days after treatment.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical observations, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 according to experimental results

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off according to OECD 423

Mortality:

No mortality occurred during the study period.

Clinical signs:

No clinical signs of toxicity were observed up to the end of the 14-day observation period.

Body weight:

No effect on body weight was noted (see Table 1).

Gross pathology:

Necropsy revealed no substance-related findings.

Table 1. Individual body weights and weekly body weight changes.

Dose level mg/kg bw	Animal number and sex	Body weight (g) at Day			Body weight gain (g) during week
		0	7	14	1	2
2000	1-0 Female	204	237	249	33	12
2000	1-1 Female	235	262	280	27	18
2000	1-2 Female	225	265	284	40	19
2000	1-0 Male	217	300	352	83	52
2000	1-1 Male	209	284	318	75	34
2000	1-2 Male	229	297	339	68	42

 

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises adequate, reliable study from a source substance with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent similar properties and behaviour (refer to endpoint discussion for further details).

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

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

Adequacy of study:

key study

Justification for type of information:

There is no data available for the acute toxicity of Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9). In order 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, read-across from a structurally related substance was 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 substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity.

The source substance Dipentaerythritol hexaesters with fatty acids C5 and C9 iso is considered to be similar to the target substance, on the basis of the structural and similar properties and/or activities. The available acute toxicity study (dermal route) for the source substance is used to predict the same endpoint for the target substance Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424-11-9).
A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: Not classified

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: Annex V

Version / remarks:

Directive 67/548

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Type of coverage:

semiocclusive

Vehicle:

other: Test material was used as supplied

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5 male animals
5 female animals

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

0 male animals
0 female animals

Clinical signs:

Signs of toxicity related to dose levels:
No signs of systemic toxicity were noted during the study.

Gross pathology:

Effects on organs:
No abnormalities were noted at necropsy. No signs of skin irritation were noted during the study. No deaths were recorded.

Other findings:

Signs of toxicity (local):
No signs of skin irritation were noted during the study.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The available information comprises adequate, reliable study from a source substance with similar structure and intrinsic properties. Read-across is justified based on common origin, common precursors and breakdown products of hydrolysis and consistent similar properties and behaviour (refer to endpoint discussion for further details).

Justification for classification or non-classification

Based on the read-across from a structurally similar substance with available data on acute oral and dermal toxicity, the target substance Dipentaerythritol hexaesters of 3,5,5-trimethylhexanoic and n-heptanoic acids (CAS 1379424 -11 -9) does not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC. Available data is, therefore, conclusive but not sufficient for classification.