Registration Dossier

Administrative data

Description of key information

Oral (OECD 401), rat: LD50 > 10000 mg/kg bw
Dermal (OECD 402), rat and rabbit: LD50 > 2000 mg/kg bw
Inhalation (OECD 403), rat, 4 h, (limit test): LC50 > 1600mg/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:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (non-GLP).
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
As described in guideline.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
10 g/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
No deaths occurred.
Clinical signs:
The only clinical sign of toxicity was piloerection.
Body weight:
No effects.
Gross pathology:
No effects.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to Guideline study (non-GLP).
Qualifier:
equivalent or similar to
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 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
1 600 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

To cover the endpoint acute toxicity of substance C16 -18AE (CAS 68439-49-6), also studies from similar substances were taken for a read-across or 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).

 

The study addressing acute oral toxicity study with C16-18AE (CAS 68439-49-6) itself was conducted according to OECD Guideline 401. In this limit test five Wistar rats per sex received 10,000 mg/kg bw. No mortalities occurred, resulting in a LD50 value of greater than 10,000 mg/kg bw. Clinical signs comprised piloerection only. Moreover, necropsy revealed no effects.

 

No data regarding acute dermal toxicity are available for C16-18AE (CAS 68439-49-6). Therefore acute dermal toxicity was addressed using structurally related read-across substances for a weight-of-evidence approach, C6-10AE (CAS 112-59-4), C6-12AE (CAS 68439-45-2), C10-16AE (CAS 68002-97-1), C12-13AE (CAS 66455-14-9), C12-15AE (CAS 68131-39-5) and C12-14AE (3EO, CAS 68439-50-9)

The first study with C6-10AE (CAS 112-59-4) equivalent to OECD Guideline 402 was carried out on five New Zealand White rabbits per sex and dose. Both sexes were dosed at 900, 1900 and 3700 mg/kg bw under occlusive conditions for 24 h, with the females receiving an additional dose of 2600 mg/kg bw. Mortalities occurred at a dose level of 1900 mg/kg bw and above, resulting in a LD50 of 2000 mg/kg bw for males and 2216 mg/kg bw for females, respectively. Moreover, necropsy revealed dark red or dark pink lungs in the deceased animals.

The second study regarding acute dermal toxicity was conducted with C6-12AE (CAS 68439-45-2). This limit test was conducted equivalent to OECD Guideline 402; however, only four Wistar rats per sex were used. The dose level of 2000 mg/kg bw was applied occlusive for 24 h and caused neither treatment-related clinical signs nor mortalities. Hence, the LD50 was determined to be greater than 2000 mg/kg bw.

The study conducted with C10-16AE (CAS 68002-97-1) was as well a limit test conducted equivalent to OECD Guideline 402. In this limit test five New Zealand White rabbits per sex received 2000 mg/kg bw for a 24 h-occluded exposure. No mortalities occurred, hence, the LD50 value was set to greater than 2000 mg/kg bw.

With C12-13AE (CAS 66455-14-9), a study according to OECD Guideline 402 was carried out on four Wistar rats per sex and dose. 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 and approximately 4000 mg/kg bw. Rats showed at all dose levels hyperactivity to stimuli. In the deceased, additional symptoms like lethargy, dyspnoea and greasy soiled fur and a progressive loss of body weight were observed.

The study conducted with C12-14AE (3EO, CAS 68439-50-9) was performed as limit test conducted similar to OECD Guideline 402. In this limit test five New Zealand White rabbits per sex received 3000 mg/kg bw for a 24 h-occluded exposure. No mortalities occurred, hence, the LD50 value was set to greater than 2000 mg/kg bw.

In the last study regarding acute dermal toxicity, a limit test with C12-15AE (CAS 68131-39-5) was conducted equivalent to OECD Guideline 402. Four Wistar rats per sex were exposed occlusive to 2000 mg/kg bw for 24 h and caused neither treatment-related clinical signs nor mortalities. Hence, the LD50 was determined to be greater than 2000 mg/kg bw.

 

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 the test substance at the calculated saturated vapour concentration of 100 mg/m³. 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 (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 (limit test). 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.


Justification for selection of acute toxicity – oral endpoint
Reliable Guideline study chosen.

Justification for selection of acute toxicity – inhalation endpoint
Study with the highest maximum achievable dose was selected.

Justification for selection of acute toxicity – dermal endpoint
No study chosen due to woe approach

Justification for classification or non-classification

According to the classification criteria of Directive 67/548/EEC and Regulation (EC) No 1272/2008 the substance does not need to be classified for acute toxicity.