Heptane

Endpoint summary

Description of key information

Oral LD₅₀ (rat) > 5000 mg/kg bw

 

Inhalation LC₅₀ (rat) > 29.9 mg/L

 

Dermal LD₅₀ (rabbit) > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Limit test with 5000 mg/kg versus 2000 mg/kg as per guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Limit test with 5000 mg/kg versus 2000 mg/kg as per guideline

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

5000 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: observations daily; weighing on initiation and on days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Mortality:

No mortality occurred in any test animal over the 14-day observation period.

Clinical signs:

other: Clinical observations noted one-hour post exposure in 8 of 10 animals included depression, salivation, wheezing, rough coat, and soft feces. Two female rats appeared normal throughout the study. All animals appeared normal from day 2 through termination

Gross pathology:

No abnormal gross pathology findings were noted in any of the animals upon necropsy.

Interpretation of results:

other: Not classified

Remarks:

Criteria used for interpretation of results: other: GHS, EU, 2007

Conclusions:

Based on the study design the test substance, Isooctane, needs not to be classified.

Executive summary:

Based on the study design the test substance, Isooctane, needs not to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Quality of whole database:

1 key read across study from a structural analogue available for assessment

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

- very limited documentation

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: unchanged (no vehicle)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

29.29 mg/L nominal
17937.5 ± 5665.92 ppm (mean analytical concentration and SD) = 73.5 mg/L ± 2.32 (re-calculated from ppm value given in study report)

No. of animals per sex per dose:

10

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: not specified, but at least 4 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 29.29 mg/L air (nominal)

Exp. duration:

4 h

Remarks on result:

other: only one concentration tested

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 73.5 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: only one concentration tested

Sex:

male/female

Dose descriptor:

LC0

Effect level:

>= 29.29 mg/L air (nominal)

Exp. duration:

4 h

Remarks on result:

other: only one concentration tested

Mortality:

No mortality occurred during the course of the study.

Clinical signs:

other: No clinical signs observed throughout the study.

Body weight:

Slight reduction of mean male body weights on day 2 post exposure, but males recovered by day 4.
Female weight changes were minimal.
All animals appeared normal throughout the study.

Gross pathology:

All animals appeared normal at terminal necropsy with the exception of one female with enlarged mandibular lymph nodes on the right side

Normal-Heptane has a low order of toxicity by the inhalation route of exposure.

Interpretation of results:

not classified

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

Based on the study design Normal-Heptane has a low order of toxicity by the inhalation route of exposure and needs not to be classified.

Executive summary:

Based on the study design Normal-Heptane has a low order of toxicity by the inhalation route of exposure and needs not to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 29.9 mg/L air

Physical form:

inhalation: vapour

Quality of whole database:

1 key study available for assessment

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study meets generally accepted scientific principles, acceptable for assessment.

Justification for type of information:

A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Only 3 animals per sex versus 5 as per guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

Only 3 animals per sex versus 5 as per guideline

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation continuous, weighing on initiation and days 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, dermal score

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred during the 14-day observation period.

Clinical signs:

other: All rabbits appeared normal throughout the study. Very slight dermal erythema was noted in all animals on day 1 after dosing, which persisted in one male and one female on day 3. All erythema had cleared by day 7. Very slight edema was noted in two males

Gross pathology:

No abnormal gross pathology was noted in any rabbits upon necropsy.

Interpretation of results:

other: not classified

Remarks:

Criteria used for interpretation of results: other: GHS, EU, 2007

Conclusions:

Based on the study design the test substance, Isooctane, needs not to be classified.

Executive summary:

Based on the study design the substance, Isooctane, needs not to be classified.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Quality of whole database:

1 key read across study from a structural analogue available for assessment

Additional information

Acute inhalation toxicity data is available for Heptane. Acute oral and dermal toxicity data is available for structural analogue 2,2,4-trimethylpentane. This data is read across to based on analogue read across and a discussion and report on the read across strategy is provided as an attachment in IUCLID Section 13.

 

Oral

 

2,2,4-trimethylpentane

In a key study (Chevron Phillips Chemicals, 1982), five male and five female Sprague-Dawley rats were exposed, orally by gavage, to a single 5000 mg/kg bw dose of 2,2,4-trimethylpentane. The animals were observed for mortality and clinical signs for the next 14 days. No animals died during the study. Clinical signs of depression, salivation, wheezing, rough coat and soft faeces were observed from one-hour post exposure until day 2. No clinical signs were noted from day 2 to termination of the study. No abnormalities were noted at necropsy. The LD₅₀ was determined to be >5000 mg/kg bw. Under the conditions of this study, 2,2,4-trimethylpentane does not need to be classified.

 

Inhalation

 

Heptane

Ten male and female Sprague-Dawley rats were exposed to Normal-Heptane via whole body inhalation at nominal concentration of 29.29 mg/L for 4 hours (similar to OECD 403). The analytical concentration was determined to be ca. 73.50 mg/L. There was no mortality during the course of the study. A slight reduction of mean male body weights was noted on day 2 post-exposure but males recovered by day 4. All animals appeared normal throughout the study and at terminal necropsy with the exception of one female observed with enlarged mandibular lymph nodes on the right side. The LC₅₀ was greater than the nominal concentration of 29.29 mg/L (Chevron Phillips, 1982).

 

Dermal

 

2,2,4-trimethylypentane 

In a key study (Chevron Phillips Chemicals, 1982), three male and three female New Zealand White rabbits were administered a single, topical 2000 mg/kg bw dose of 2,2,4-trimethylpentane. The test material remained in contact with the skin for 24 hours. Animals were observed for mortality and clinical signs for the next 14 days. No animals died during the study. No clinical signs of toxicity were observed. Very slight dermal erythema was noted in all animals on day 1, and persisted to day 3 in one male and one female. All erythema had cleared by day 7. Very slight oedema was noted in two males and one female on day 1 and cleared by day 3. Epidermal scaling was noted in one female on day 10. No abnormalities were noted at necropsy. The LD₅₀ was determined to be >2000 mg/kg bw. Under the conditions of this study, 2,2,4-trimethylpentane does not need to be classified.

Justification for classification or non-classification

Based on available substance specific and read across data, Heptane is minimally toxic via ingestion where the LD₅₀ is >5000 mg/kg bw, via dermal exposure where the LD₅₀ is >2000 mg/kg bw, and by inhalation where the LC₅₀ is > 29.29 mg/L.  These findings do not warrant classification under the new Regulation (EC) 1272/2008 on classification, labeling and packaging of substances and mixtures (CLP).

 

Heptane is classified under EU CLP guidelines as STOT Single Exposure Category 3 (narcosis) based on non-lethal narcotic effects observed in acute inhalation exposure.

Heptane is classified under EU CLP guidelines as a Category 1 aspiration hazard based on its physical and chemical properties (hydrocarbon fluid, viscosity ≤ 20.5 mm²/s).