Heptanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol pentanoate

Endpoint summary

Description of key information

In conclusion, by read-across, heptanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol pentanoate is considered to be of low acute toxicity by the oral and the dermal routes. An acute inhalation toxicity study was not conducted because exposure to humans via the inhalatory route is unlikely to occur.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Study period:

6 November 1990 - 20 November 1990

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study conducted according to OECD Guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Limited details on test compound

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: ICO: OFA-SD (IOPS Caw)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Iffa Crédo, France
- Age at study initiation: 6 weeks
- Weight at study initiation: 173 +/- 3 g for males and 144 +/- 7 g for females
- Housing: 5 animals per polycarbonate cage (48x27x20 cm)
- Fasting period before study: 18 h before until 4 h after dosing
- Diet (e.g. ad libitum): ad libitum (Rats - Mice substance ref. A04 C)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.13 ml taking into account the specific gravity of 0.94.

Doses:

2000 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, weighing on days 1, 5, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: gross pathology

Statistics:

Not applicable

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: Hypokinesia was observed 2 and 4 h after treatment. From day 2 to the end of the study, no clinical signs were observed.

Gross pathology:

No apparent abnormalities

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study in rats, the LD50 for read-across substance, decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate was > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study conducted in accordance with OECD guideline therefore study is categorised as Klimisch 1 study and assessment factor for the quality of whole database is 1.

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:

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

Adequacy of study:

key study

Study period:

19 June 1996 to 5 July 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to OECD Guideline with restrictions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP, Pennsylvania
- Age at study initiation: Young adults (at least 8 weeks)
- Weight at study initiation: males: 2.4-3.1 kg, females 2.5-2.7 kg
- Housing: Individually housed in suspended, stainless steel cages with wire mesh bottoms
- Diet (e.g. ad libitum): Lab Rabbit Diet HF, No 5326, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: males 58 d, females 60 d


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 12 cm x 14 cm, clipped area of the dorsal trunk surface
- % coverage: approx. 10% of body surface
- Type of wrap if used: Gauze secured with tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiping with distilled water
- Time after start of exposure: 24 h

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:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: mortality: twice daily; dermal observations: 1, 24, 48 and 72 h after bandage removal; observations of pharmacologic and toxicologic signs: 1, 2 and 4 h after dosing and daily thereafter for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: check of clinical signs and body weight

Statistics:

Not required

Preliminary study:

Not applicable

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: No adverse effects observed

Gross pathology:

No adverse effects observed

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute dermal toxicity study in rats, the LD50 for read-across substance, decanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol octanoate was > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study conducted in accordance with OECD guideline therefore categorised as Klimisch 1 study and assessment factor for the quality of whole database is 1.

Additional information

Two acute oral toxicity studies have been conducted in rats with read-across substance, decanoic acid, ester with 2-ethyl-2- (hydroxymethyl)-1,3-propanediol octanoate. Both studies were conducted in accordance with OECD Guideline 401. In the key acute oral toxicity study in rats, LD50 was determined to be > 2000 mg/kg bw. The supporting study provided an oral LD50 > 5000 mg/kg.

In an acute dermal toxicity study in rats, the LD50 for read-across substance, decanoic acid, ester with 2-ethyl-2-(hydroxymethyl) -1,3-propanediol octanoate was determined to be > 2000 mg/kg bw.

An acute inhalation toxicity study was not conducted because the test substance has a very low vapour pressure so the potential for the generation of inhalable forms is low therefore exposure to humans via the inhalatory route is unlikely to occur.

In conclusion, by read-across, heptanoic acid, ester with 2-ethyl-2-(hydroxymethyl)-1,3-propanediol pentanoate is considered to be of low acute toxicity by the oral and the dermal routes.

Justification for selection of acute toxicity – oral endpoint
Study with lowest NOAEL has been selected as worst case.

Justification for selection of acute toxicity – inhalation endpoint
The test substance has a very low vapour pressure so the potential for the generation of inhalable forms is low therefore exposure to humans via the inhalatory route is unlikely to occur.

Justification for selection of acute toxicity – dermal endpoint
Only 1 study is available.

Justification for classification or non-classification

The above studies have all been ranked reliability 1 according to the Klimisch et al system. This ranking was deemed appropriate because the studies were conducted according to recognised test methods. Sufficient dose ranges and numbers are detailed; hence they are appropriate for use based on reliability and animal welfare grounds.

The above results triggered no classification under the Dangerous Substance Directive (67/548/EEC) and the CLP Regulation (EC No 1272/2008).  However, testing on the physico-chemical endpoints indicate that the substance has a kinematic viscosity of 11.7 mm²/s at 40 °C, which triggers classification as Aspiration Toxicity Category 1 under the CLP Regulation.