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Description of key information

Oral (OECD 401), rat: LD50 > 2000 mg/kg bw
Dermal (OECD 402), rabbit: LD50 > 2000 mg/kg bw
Inhalation (OECD 403), rat, 4 h, (limit test): LC50 > 1600 mg/m³ (maximum technically attainable concentration)

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
Justification for type of information:
Refer to the category justification provided in IUCLID Section 13
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Effect level:
> 5 050 mg/kg bw
Remarks on result:
other: Source: CAS 68002-97-1, Sasol, 1992a
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Conclusions:
A LD50 of > 5050 mg/kg bw was determinied for male and female rats.
Executive summary:

The acute oral toxicity of the target substance is estimated based on an adequate and reliable in vivo study of a structural analogue source substances. A LD50 value of > 5050 mg/kg bw has been determined for male and female rats. Therefore, a LD50 value of > 2000 mg/kg bw for the target substance is considered for the hazard assessment and C&L purposes. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
The available information comprises an adequate and reliable (Klimisch score 1) study from a source substance with similar structures and intrinsic properties. Read-across is justified based on a common metabolic breakdown of target and source substances and consistent trends in environmental fate, ecotoxicological and toxicological properties. The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, Item 8.5, in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
weight of evidence
Justification for type of information:
Refer to the category justification provided in IUCLID Section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 600 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Source, WoE, 68002-97-1, 1982a
Remarks:
Maximum attainable concentration.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 100 mg/m³ air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Source, WoE, 112-59-4, 1987
Remarks:
Effect level represents calculated saturated vapour pressure.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The inhalation LD50 values determined range from > 100 mg/m3 air to > 1600 mg/m3 air for male and female rats. The values represent the maximum attainable concentration and the calculated saturated vapour pressure of the test materials, respectively.
Executive summary:

The acute inhalation toxicity of the target substance is estimated based on two adequate and reliable in vivo studies of structural analogue source substances. The inhalation LD50 values determined range from > 100 mg/m3air to > 1600 mg/m3air for male and female rats. The values represent the maximum attainable concentration and the calculated saturated vapour pressure of the test materials, respectively. Therefore, no hazard for the target substance is identified and C&L is set accordingly. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute inhalation toxicity

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
not specified
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:
As described in guideline.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
6 h
Concentrations:
Saturated vapour atmosphere (calculated)
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 100 mg/m³ air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: Effect level represents calculated saturated vapour pressure.
Mortality:
No treatment-related effects.
Clinical signs:
other: No treatment-related effects.
Body weight:
No treatment-related effects.
Gross pathology:
No treatment-related effects.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
As described in guideline.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.90 ± 1.82
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
1.60 mg/L air, corresponding to 1600 mg/m3
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.6 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Maximum attainable concentration.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1 600 mg/m³ air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Maximum attainable concentration.
Mortality:
No deaths occurred.
Clinical signs:
other: Slight nasal discharge and lacrimation during exposure as well as slight, red nasal discharge postexposure.
Body weight:
Slight reduction in the mean body weight gain was noted in females on Day 14 postexposure.
Gross pathology:
The following gross pathology was noted at the terminal sacrifice: one male had dilated, fluid filled left renal pelvis; one male and one female had enlarged mandibular lymph nodes; another female had dilated right renal pelvis containing firm, granular, white material and uterine horns distended with clear fluid; and one female had a dilated right renal pelvis containing white granular fluid. Three of five males and two of five females had no observable abnormal lesions at the terminal sacrifice.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
1 600 mg/m³
Quality of whole database:
The available information comprises adequate and reliable (Klimisch score 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on a common metabolic breakdown of target and source substances and consistent trends in environmental fate, ecotoxicological and toxicological properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
weight of evidence
Justification for type of information:
Refer to the category justification provided in IUCLID Section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Source, WoE, 68002-97-1, 1982b
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Source, WoE, 68439-50-9 (3EO), 1990a
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: Source, WoE, 66455-14-9, 1979
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Source, WoE, 68131-39-5, 1978
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
Individual LD50 values determined in male and female rabbits range from > 2000 mg/kg bw to > 3000 mg/kg bw.
Executive summary:

The acute dermal toxicity of the target substance is estimated based on adequate and reliable in vivo studies of structural analogue source substances. Individual LD50 values determined range from > 2000 mg/kg bw to > 3000 mg/kg bw for male and female rabbits. Therefore, a LD50 value of > 2000 mg/kg bw for the target substance is considered for the hazard assessment and C&L purposes. As explained in the category justification, the differences in molecular structure between the target and the source substances are unlikely to lead to differences in the acute dermal toxicity.

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
According to Guideline.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
1000, 2000, 4000 mg/kg bw
No. of animals per sex per dose:
4
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Abraded skin.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
As described in guideline.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No deaths occurred.
Clinical signs:
No data about systemic toxicity.
Body weight:
No data.
Gross pathology:
No data.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Only 4 animals per sex
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:
As described in guideline.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
4
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
10 instead of 5 animals used, Occlusive conditions, Limit dose was 3000 instead of 2000 mg/kg bw
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Hare-Marland, New Jersey, USA
- Housing: Individually
- Weight at study initiation: 2 to 3 kg
- Diet (ad libitum): Purina Rabbit Ration
- Water (ad libitum): Tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3
- Humidity (%): 30 to 70
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Type of wrap if used: Animals were wrapped with rubber dam and an elastic bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
The test site was not rinsed after removal of the patch.
Duration of exposure:
24 h
Doses:
3000 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: Observations were recorded daily through Day 14. Body weights were recorded at initiation and on Days 7 and 14.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
No mortalities occured.
Clinical signs:
Clinical signs observed during the Limit Test included poor grooming (observed from Day 2 to 5 in all animals), decreased muscle tone (observed from Day 6 to 8 in maximum 2 males and 3 females) and dyspnea (observed from Day 3 to 10 in maximum 3 animals of each sex).
Body weight:
Mean body weights of day 7 were decreased compared to Day 1 but recoverd by Day 14.
Gross pathology:
Terminal necropsy revealed mottled and pale lung in one female and multiple cysts in the ovaries of two females.
Other findings:
Slight to severe erythema and edema and green discoloration of fur surrounding application site were observed. Necrosis, fissuring, and sloughing of the skin at application site was also observed.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
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 and reliable (Klimisch score 1 and 2) studies from various source substances with similar structures and intrinsic properties. Read-across is justified based on a common metabolic breakdown of target and source substances and consistent trends in environmental fate, ecotoxicological and toxicological properties. The selected studies are thus sufficient to fulfil the standard information requirements set out in Annex VIII, Item 8.5, in accordance with Annex XI, Item 1.5, of Regulation (EC) No. 1907/2006.

Additional information

To cover the endpoint acute toxicity of decan-1-ol, ethoxylated (1 -2.5 EO) (CAS 26183-52-8), studies from similar substances were taken for read-across of key information or in a Weight-of-Evidence approach. Read-across is justified because the length of the alkyl chain does not exert any meaningful influence on acute toxicity, whereas the degree of ethoxylation is of more importance. Up to the level of EO = 4, which includes all read-across substances, the toxicity is low (HERA, 2009).

 

Acute oral toxicity

The study addressing acute oral toxicity with C10-16AE (CAS 68002-97-1) was conducted according to OECD Guideline 401 (Sasol, 1992a). In this limit test five Sprague-Dawley rats per sex received 5050 mg/kg bw. No mortalities occurred, resulting in a LD50 value of greater than 5050 mg/kg bw. Clinical signs comprised activity decrease, diarrhoea, piloerection and polyuria. Moreover, necropsy revealed no effects.

Acute inhalation toxicity

There are two studies available addressing acute inhalation toxicity, being performed with C6-10AE (CAS 112-59-4) and C10-16AE (CAS 68002-97-1) and equivalent to OECD Guideline 403.

In the first study five Wistar rats per sex were exposed for a period of 6 h to a vapour of C6-10AE (EO2, CAS 112-59-4) at the calculated saturated vapour concentration of 100 mg/m³ (Ballantyne, 1987). No mortality or clinical signs occurred during the exposure period. The LC50 was determined to be greater than 100 mg/m³ for exposure to an aerosol of the test substance for 6 h.

In the second study with C10-16AE (EO2, CAS 68002-97-1) five Sprague Dawley rats/sex were exposed for a period of 4 h to an aerosol of the test substance at a concentration of 1600 mg/m³ (corresponding to 1.6 mg/L), which is the maximum technically attainable concentration of the test substance with a MMAD < 4 µm (Sasol, 1982a). No mortality occurred during the exposure or the 14-day observation period. The animals demonstrated clinical signs of toxicity like slight nasal discharge and lacrimation during exposure as well as slight, red nasal discharge post-exposure. The LC50 was determined to be greater than 1600 mg/m³ for exposure to an aerosol of the test substance for 4 h.

Acute dermal toxicity

The study with C10-16AE (EO2, CAS 68002-97-1) was conducted equivalent to OECD Guideline 402 (Sasol, 1982b) as limit test. In this study, five New Zealand White rabbits per sex were treated with 2000 mg/kg bw for 24 h under occlusive conditions. No mortalities occurred, hence, the LD50 value was greater than 2000 mg/kg bw.

With C12-13AE (EO2, CAS 66455-14-9), a study according to OECD Guideline 402 was carried out on four Wistar rats per sex and dose (Shell, 1979). Both sexes were dosed at 1000, 2000 and 4000 mg/kg bw under occlusive conditions for 24 h. Mortalities occurred at a dose level of 2000 mg/kg bw and above, resulting in a LD50 of greater than 2000 mg/kg bw.

The study conducted with C12-14AE (EO3, CAS 68439-50-9) was performed as limit test similar to OECD Guideline 402 (Huntsman, 1990a). In this limit test five New Zealand White rabbits per sex were treated with 3000 mg/kg bw for 24 h under occlusive conditions. No mortalities occurred, hence, the LD50 value was set to greater than 3000 mg/kg bw.

In the last study regarding acute dermal toxicity, a limit test with C12-15AE (EO3, CAS 68131-39-5) was conducted equivalent to OECD Guideline 402 (Shell, 1978). Four Wistar rats per sex were treated with 2000 mg/kg bw for 24 h under occlusive conditions. No treatment-related clinical signs or mortalities were observed. Hence, the LD50 was greater than 2000 mg/kg bw.

Justification for classification or non-classification

According to the classification criteria of Regulation (EC) No. 1272/2008 the substance does not need to be classified for acute toxicity.